Verification of TMDOCK generated dimers for agreement with experimental data

Parallel homodimers of bitopic proteins included into the Membranome 2.0 database were generated by the TMDOCK method [1]. The method ranks the models based on the calculated Gibbs free energy of helix association (ΔGasc) and other parameters. Free energy components include van der Waals, hydrogen bonding, and electrostatic interactions, side chain conformational entropy, and solvation energy in the anisotropic environment. The accuracy and reliability of TMDOCK predictions has been previously justified by successful prediction of 26 experimental structures of homodimers with r.m.s.d. below 3.3 Å.

TMDOCK predicts not only functionally relevant dimers, but also transient dimers formed due to high propensity of TM α-helices of bitopic proteins to aggregate in the lipid bilayer. For 6,039 bitopic proteins from the database, TMDOCK predicted 5,670 homodimers with ΔGasc< -1kcal/mol and 4,858 homodimers with ΔGasc<-3 kcal/mol.

Selection of presumably functionally relevant dimers was based on the following criteria:
1. Low helix association energy. For superfamilies with multiple dimer-forming proteins, dimers with ΔGasc<-1 kcal/mol were selected for analysis. For “singleton” superfamilies with one or two dimer-forming proteins, the stricter cutoff was used. (ΔGasc<-3 kcal/mol).
2. Conservation of dimerization modes for homologous proteins. A supplementary program was developed for pairwise structural superposition and sequence comparison of a set of multi-model PDB files representing proteins from the same superfamily. Common dimerization modes were automatically identified in different proteins based on the following requirements: low pairwise r.m.s.d, similar crossing angles, crossing point located at the similar depth in the membrane, and 35-80% sequence identity of overlapping structures. TM helices with sequence identity >80% usually formed similar dimers.
3. Adequate hydrophobic thickness. Spatial positions in membranes of models with common dimerization modes were optimized by PPM. Dimers were rejected if their hydrophobic thicknesses deviated by more than 6 Å from the average thickness of membrane of residence.
4. Close packing. Models with poor helix packing were rejected.
5. Formation of interhelical hydrogen bonds. Polar residues within TM segments tend to form interhelical hydrogen bonds, thus stabilizing dimer structure. Models with polar residues (N,Q,H,D,E,K,R) not forming H-bonds and facing to the lipid acyl chain region were rejected.

Based on these criteria, 2,129 homodimers were included into the Membranome database. The included dimers were further verified for agreement with published experimental data on homodimerization of 598 bitopic proteins (Tables 1-5). These data include: (a) helix association modes proposed based on from NMR or mutagenesis experiments for 52 proteins (Table 1 and 2); (b) evidence of TM helix association by TOXCAT or other methods for 185 proteins (Table 3); (c) crystal structures of homodimers of water-soluble domains of 161 different bitopic proteins (Table 4); and (d) UniProt annotation of 304 bitopic proteins as forming homodimers (Table 5).

Table 1. Bitopic proteins from Membranome 2.0 with experimentally determined 3D models of transmembrane homodimers
Family code Protein name UniProt code References PDB1 Type2 Comment3 Beta-type
platelet-derived growth
factor receptor
PGFRB_HUMAN [2, 3, 4, 5] 2l6w L -(R)4 Epidermal growth factor
EGFR_HUMAN [2, 6, 7, 8, 9, 10, 11, 12, 13] 2m0b, 2m20 R + Receptor
tyrosine-protein kinase
ERBB2_HUMAN [2, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20] 2jwa, 2n2a R + Receptor
tyrosine-protein kinase
ERBB3_HUMAN [2, 8, 9, 12, 13, 21] 2l9u L -(R)4 Receptor
tyrosine-protein kinase
ERBB4_HUMAN [2, 8, 9, 12, 13] 2l2t R + Ephrin type-A receptor 1 EPHA1_HUMAN [2, 22] 2k1k, 2k1l R + Ephrin type-A receptor 2 EPHA2_HUMAN [2, 23] 2k9y L -(R)4 Fibroblast growth factor
receptor 3
FGFR3_HUMAN [2, 24, 25, 26, 27] 2lzl L -(R)4 Vascular endothelial
growth factor receptor 2
VGFR2_HUMAN [2, 28] 2m59, 2meu L + Tumor necrosis factor
receptor superfamily
member 16
TNR16_HUMAN [29, 30, 31] 2mic, 2mjo L +5 Toll-like receptor 3 TLR3_HUMAN [32, 33] 2mka, 2mk9 R, L + T-cell surface
glycoprotein CD3 zeta
CD3Z_HUMAN [34] 2hac L + Amyloid beta A4 protein A4_HUMAN [35, 36, 37, 38, 39, 40, 41] 2lz3, 2lz4, 2loh R, L + TYRO protein tyrosine
kinase-binding protein
TYOBP_HUMAN [42, 43] 2l34, 4wo1, 4wol L + Glycophorin-A GLPA_HUMAN [44, 45, 46, 47] [48, 49, 50, 51] 5eh4 R + BCL2/adenovirus E1B 19
kDa protein-interacting
protein 3
BNIP3_HUMAN [52, 53, 54, 55, 56] 2ka1, 2ka2, 2j5d R +

1 Representative PDB files for significantly different 3D structures

2 Type of the dimeric association in NMR models: “L” is left handed Leu-zipper-like association with helix crossing angle of +10 to +30°; “R” is right-handed association through GxxxG-like motif with helix crossing angle of -60 to -30°

3 Sign “+” indicates that the the top-ranked calculated model was in agreement with experimental structure

4 The calculated preferable helix arrangement was “R” through GxxxG-like motif, similar to that in most proteins from the family. The NMR-like models with left-handed helix arrangement were reproduced in calculations, but with the higher association energy

5 The sets of calculated low-energy association modes are partly different for human and rat sequences. The 3D models of homodimer included in Membranome were calculated for rat sequence to facilitate comparison with NMR model from the PDB (2mic).

Table 2. Bitopic proteins from Membranome with specific modes of transmembrane homodimerization suggested in the literature based on experimental data (in addition to proteins included in Table 1).
Family code Protein name Dimer type1 UniProt code References Comment2 Key residues9 Receptor-type tyrosine-protein
phosphatase eta
R PTPRJ_HUMAN [57] + G979, G983, G987 Erythropoietin receptor L EPOR_HUMAN [58, 59, 60, 61] +3 L234, S238, L241, A245 Thrombopoietin receptor L TPOR_HUMAN [62, 63, 64] + H499 T-cell surface glycoprotein CD4 R CD4_HUMAN [65] +4 G402, G406 Carcinoembryonic
antigen-related cell adhesion
molecule 1
R CEAM1_HUMAN [66, 67, 68] + G432, G436 Proto-oncogene tyrosine-protein
kinase receptor Ret
L RET_HUMAN [2, 69, 70] + S649, S653 Atypical kinase ADCK3,
L ADCK3_HUMAN [71] + A215, G219, G223 AarF domain-containing protein
kinase 4
L ADCK4_HUMAN [71] + A215, G219, G223 Leucine-rich repeat receptor-like
kinase SOBIR1
R SBIR1_ARATH [72] + G274, G278, G282 Serine/threonine-protein
kinase-like protein ACR4
L ACR4L_ARATH [73, 74] -5 Epithelial discoidin
domain-containing receptor 1
L DDR1_HUMAN [2, 68, 75] +6 A425, L432 Integrin alpha-IIb R ITA2B_HUMAN [76, 77, 78, 79] + V1002, G1003, G1006, G1007 Integrin beta-3 R ITB3_HUMAN [80, 81] -8 Neuropilin-1 R NRP1_HUMAN [12, 82, 83] + G868, G872, G876 Kit ligand L SCF_HUMAN [84] +6 S225, G229, Y236 Syndecan-2 R SDC2_HUMAN [86, 87, 88] + A149, G153, G157 Syndecan-3 R SDC3_HUMAN [88, 89] + A149, G153, G157 Syndecan-4 R SDC4_HUMAN [86, 88] + A149, G153, G157 Platelet glycoprotein Ib beta chain L GP1BB_HUMAN [90, 91] + Q129, H139 HLA class II histocompatibility
antigen, DRB1-15 beta chain
R 2B1F_HUMAN [92] + G234, G238 HLA class II histocompatibility
antigen, DRB1-10 beta chain
R 2B1A_HUMAN [93] + G234, G238 HLA class II histocompatibility
antigen, DRB1-1 beta chain
R 2B11_HUMAN [92] + G234, G238 HLA class II histocompatibility
antigen, DQ alpha 1 chain
R DQA1_HUMAN [68, 92] + G223, G227 B-cell antigen receptor
complex-associated protein beta
L CD79B_HUMAN [94] + Q165 CD40 ligand R,L CD40L_HUMAN [94] + Q35 Myelin protein P0 R MYP0_HUMAN [68, 95] + G126, V127, G134, G138 Cadherin-1 R CADH1_HUMAN [96] -7 MGA2 transcription factor R MGA2_YEAST [97] +6 W1042, F1053, Y1056 Cell division protein FtsB L FTSB_ECOLI [98, 99] + Q16 Sec-independent protein
translocase protein TatA
L TATA_ECOLI [100] + Q8 Vesicle-associated membrane
protein 2
L VAMP2_HUMAN [101, 102, 103, 104, 105] + C103, I110 Sodium/potassium-transporting
ATPase subunit beta-1
R AT1B1_HUMAN [106] + G44, G48, G52 Cytochrome b559 subunit beta R PSBF_ARATH [107, 108, 109] + V25, V29, A33 Sulfhydryl oxidase 2 L QSOX2_HUMAN [110, 111] + Y668, S771, S772, L775, M776 Galactoside
3(4)-L-fucosyltransferase 3
L FUT3_HUMAN [94] + Q23 Dipeptidyl peptidase 4 R DPP4_HUMAN [112] + L11, A15

1 Type of helix arrangement in calculated models: L, left-handed; R, right-handed

2 Sign “+” indicates that the the top-ranked model was in agreement with experimental data

3 Mode of association was changed when calculated for a sequence used in experimental study (it is different from the sequence in Membranome) and became consistent with interface identified by Asn-scanning mutagenesis.

4 Experimental study was conducted for mouse orthologue with slightly different sequence. The results of calculations with TMDOCK are consistent with experimental findings that Gly mutation leads to the loss of function, but does not affect the strength of dimerization. According to calculations, the helices remain strongly associated in the mutant, but switch from the R-type to the L-type of the dimer.

5 No specific dimerization interface was suggested in experimental study.

6 Model most consistent with mutagenesis data was ranked by TMDOCK as #2.

7 TOXCAT studies were performed for the short peptide and indicated L-type dimerization mode [96], while calculations for complete protein sequence resulted in the R-type dimer, similar to that in other family members

8 The model was consistent only with a small subset of interfacial residues proposed in the experimental study. The discrepancies could be due to multiple modes of association found for the transmembrane helices including formation of a homotrimer [80].

9 Residues involved in dimerization interface according to both mutagenesis studies and computational models.

Table 3. Bitopic proteins from Membranome whose TM segments were studied for homodimerization by TOXCAT or other similar methods (in addition to proteins included in Tables 1 and 2).
Family code Protein name Type UniProt code References Exp. Calc.1 Receptor-type tyrosine-protein phosphatase C R PTPRC_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase delta R PTPRD_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase F R PTPRF_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase gamma L PTPRG_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase S R PTPRS_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase zeta L PTPRZ_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase H R PTPRH_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase O L PTPRO_HUMAN [57, 113] + + Receptor-type tyrosine-protein phosphatase alpha L PTPRA_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase epsilon L PTPRE_HUMAN [57] + + Phosphatidylinositol
phosphatase PTPRQ
R PTPRQ_HUMAN [57] + + Receptor-type tyrosine-protein
phosphatase R
R PTPRR_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase N2 R PTPR2_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase N R PTPRN_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase kappa R PTPRK_HUMAN [57, 68] + + Receptor-type tyrosine-protein phosphatase mu R PTPRM_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase T R PTPRT_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase U R PTPRU_HUMAN [57] + + Receptor-type tyrosine-protein phosphatase beta R PTPRB_HUMAN [57] w +w Fc receptor-like protein 3 R FCRL3_HUMAN [111] + + Prolactin receptor R PRLR_HUMAN [114] + + Interleukin-12 receptor subunit beta-1 R I12R1_HUMAN [115] + + Interleukin-6 receptor subunit beta L IL6RB_HUMAN [116] + + Interleukin-27 receptor subunit alpha L I27RA_HUMAN [68] + +(no) Interleukin-6 receptor subunit beta R IL6RA_HUMAN [116] + + Interleukin-2 receptor subunit beta R IL2RB_HUMAN [117] + + Cytokine receptor common subunit gamma L IL2RG_HUMAN [117] + + Interleukin-9 receptor R IL9R_HUMAN [117] + +(no) Leukocyte immunoglobulin-like receptor subfamily B member 1 R LIRB1_HUMAN [68] + + Killer cell immunoglobulin-like receptor 2DL5A L KI2LA_HUMAN [68] + + Killer cell immunoglobulin-like receptor 2DS1 R KI2S1_HUMAN [68] + + Killer cell immunoglobulin-like receptor 3DL1 L KI3L1_HUMAN [68] + + CMRF35-like molecule 8 L CLM8_HUMAN [68] + + Polymeric immunoglobulin receptor R PIGR_HUMAN [118] + + Macrophage colony-stimulating factor 1 receptor L CSF1R_HUMAN [2] + + Receptor-type tyrosine-protein kinase FLT3 R FLT3_HUMAN [2] + + Mast/stem cell growth factor receptor Kit L KIT_HUMAN [2] + + Platelet-derived growth factor receptor alpha R PGFRA_HUMAN [2] + + Ephrin type-A receptor 3 R EPHA3_HUMAN [2] + + Amyloid beta A4 protein R EPHA4_HUMAN [2] + + Ephrin type-A receptor 5 R EPHA5_HUMAN [2] + + Ephrin type-A receptor 6 R EPHA6_HUMAN [2] + + Ephrin type-A receptor 7 R EPHA7_HUMAN [2] + + Ephrin type-A receptor 8 R EPHA8_HUMAN [2] + + Ephrin type-A receptor 10 R EPHAA_HUMAN [2] + + Ephrin type-B receptor 1 R EPHB1_HUMAN [2] + + Ephrin type-B receptor 2 R EPHB2_HUMAN [2] + + Ephrin type-B receptor 3 R EPHB3_HUMAN [2] + + Ephrin type-B receptor 4 R EPHB4_HUMAN [2] + + Ephrin type-B receptor 6 R EPHB6_HUMAN [2] + + Fibroblast growth factor receptor 1 R FGFR1_HUMAN [2, 119] + + Fibroblast growth factor receptor 2 R FGFR2_HUMAN [2, 26, 120] + + Fibroblast growth factor receptor 4 R FGFR4_HUMAN [2] + + Insulin-like growth factor 1 receptor R IGF1R_HUMAN [2] + + Insulin receptor R INSR_HUMAN [2, 29, 121, 122] + + Insulin receptor-related protein R INSRR_HUMAN [2, 29, 123] + + Tyrosine-protein kinase transmembrane receptor ROR1 L ROR1_HUMAN [2] + +(no) Tyrosine-protein kinase transmembrane receptor ROR2 L ROR2_HUMAN [2] + +(no) Tyrosine-protein kinase receptor Tie-1 L TIE1_HUMAN [2, 122] + + Angiopoietin-1 receptor L TIE2_HUMAN [2, 122] + + Tyrosine-protein kinase Mer R MERTK_HUMAN [2] + + Tyrosine-protein kinase receptor TYRO3 R TYRO3_HUMAN [2] + + Tyrosine-protein kinase receptor UFO R UFO_HUMAN [2] + + Hepatocyte growth factor receptor R MET_HUMAN [2] + + Macrophage-stimulating protein receptor L RON_HUMAN [2] + + Serine/threonine-protein kinase LMTK1 L LMTK1_HUMAN [2] + + Serine/threonine-protein kinase LMTK2 L LMTK2_HUMAN [2] + + Serine/threonine-protein kinase LMTK3 R LMTK3_HUMAN [2] + + Serine/threonine-protein kinase/endoribonuclease IRE1 L ERN1_HUMAN [124] + + Vascular endothelial growth factor receptor 1 L VGFR1_HUMAN [2] + + Vascular endothelial growth factor receptor 3 L VGFR3_HUMAN [2] + + Muscle, skeletal receptor tyrosine protein kinase R MUSK_HUMAN [2] + + Tyrosine-protein kinase RYK R RYK_HUMAN [2, 125] + + Tyrosine-protein kinase STYK1 R STYK1_HUMAN [2] + + Atrial natriuretic peptide receptor A L ANPRA_HUMAN [126] + + Discoidin domain-containing receptor 2 L DDR2_HUMAN [2] + + High affinity nerve growth factor receptor R NTRK1_HUMAN [2, 127] + + BDNF/NT-3 growth factors receptor R NTRK2_HUMAN [2, 127] + + NT-3 growth factor receptor R NTRK3_HUMAN [2] + + ALK tyrosine kinase receptor L ALK_HUMAN [2] + + Leukocyte tyrosine kinase receptor R LTK_HUMAN [2, 122] + + Inactive tyrosine-protein kinase 7 R PTK7_HUMAN [2] + + Proto-oncogene tyrosine-protein kinase ROS R ROS1_HUMAN [2] + +(no) Macrosialin - CD68_HUMAN [68] - - C-type lectin domain family 10 member A L CLC10_HUMAN [68, 111] + + C-type lectin domain family 10 member A L CL12A_HUMAN [111] + + C-type lectin domain family 4 member D L CLC4D_HUMAN [111] + + Chondrolectin R CHODL_HUMAN [111] + + Stabilin-1 R STAB1_HUMAN [99] + + Apical endosomal glycoprotein L AEGP_HUMAN [68] + + Toll-like receptor 1 L TLR1_HUMAN [32] + + Toll-like receptor 2 L TLR2_HUMAN [32] + + Toll-like receptor 4 L TLR4_HUMAN [32] + + Toll-like receptor 5 L TLR5_HUMAN [32] + + Toll-like receptor 6 L TLR6_HUMAN [32] + + Toll-like receptor 7 L TLR7_HUMAN [32] + + Toll-like receptor 8 L TLR8_HUMAN [32] + + Toll-like receptor 9 R TLR9_HUMAN [32, 129] + + Toll-like receptor 10 L TLR10_HUMAN [32] + + Integrin alpha-M R, L ITA7_HUMAN [130] + +(no) Integrin alpha-7 R ITA7_HUMAN [68] + + Integrin alpha-1 L, R ITA1_HUMAN [68] + +(no) Integrin beta-1 L, R ITB1_HUMAN [68] + + Integrin beta-2 R ITB2_HUMAN [130] + +(no) Anthrax toxin receptor 1 L ANTR1_HUMAN [131] + + Neuropilin-2 L NRP2_HUMAN [12] + + Plexin-A1 R PLXA1_HUMAN [12, 83] + + Plexin-B1 R PLXB1_HUMAN [12] + + Plexin-A2 L PLXA2_HUMAN [12] + + Amyloid beta A4 protein R PLXA4_HUMAN [132] + + Syndecan-1 R SDC1_HUMAN [88] + + Leucine-rich repeat-containing protein 32 L LRC32_HUMAN [111] + + SLIT and NTRK-like protein 4 R SLIK4_HUMAN [68] + + Platelet glycoprotein Ib alpha chain L, R GP1BA_HUMAN [91] - +(no) Platelet glycoprotein IX R GPIX_HUMAN [91] - +w HLA class I histocompatibility antigen, A-2 alpha chain R 1A02_HUMAN [68] + + HLA class II histocompatibility antigen, DO beta chain R DOB_HUMAN [68] + + HLA class II histocompatibility antigen, DP alpha 1 chain L DPA1_HUMAN [68] + + HLA class II histocompatibility antigen, DO alpha chain R DOA_HUMAN [68] + + HLA class II histocompatibility antigen, DM alpha chain R DMA_HUMAN [68] + + HLA class II histocompatibility antigen gamma chain L HG2A_HUMAN [133, 134] + + B-cell antigen receptor complex-associated protein alpha chain - CD79A_HUMAN [94] - - Neuropilin and tolloid-like protein 2 R NETO2_HUMAN [133, 134] + + Protein GAPT L GAPT_HUMAN [68] + + Mucin-4 R MUC4_HUMAN [12, 13] + + Sialic acid-binding Ig-like lectin 7 R SIGL7_HUMAN [68] + + Myeloid cell surface antigen CD33 R CD33_HUMAN [68] + + Sialic acid-binding Ig-like lectin 11 R SIG11_HUMAN [68] + + Coxsackievirus and adenovirus receptor R CXAR_HUMAN [68] + + CXADR-like membrane protein R CLMP_HUMAN [68] + + Neural cell adhesion molecule L1 R L1CAM_HUMAN [12] + + Kin of IRRE-like protein 3 R KIRR3_HUMAN [68] + + Cell adhesion molecule 2 R CADM2_HUMAN [68] + + Cell adhesion molecule 3 R CADM3_HUMAN [68] + + Cadherin-24 R CAD24_HUMAN [68] + + Cadherin-3 R CADH3_HUMAN [68] + + Cadherin-7 R CADH7_HUMAN [68] + + Calsyntenin-1 L CSTN1_HUMAN [111] + + Desmoglein-2 L DSG2_HUMAN [68] + + Protocadherin gamma-B4 L PCDGG_HUMAN [68] + + Epsilon-sarcoglycan L SGCE_HUMAN [111] + + Bone marrow stromal antigen 2 L BST2_HUMAN [135] + + Leucine-rich repeat TM neuronal protein 3 L LRRT3_HUMAN [111] + + Leucine-rich repeat and fibronectin type-III domain-containing protein 4 R LRFN4_HUMA [68] + + L-selectin L LYAM1_HUMAN [136] - +w Multiple epidermal growth factor-like domains protein 9 R MEGF9_HUMAN [68] + + Nesprin-1 L SYNE1_HUMAN [68] + + Cell division protein ZipA R, L ZIPA_ECOLI [99] + +(no) Cell division protein FtsL L FTSL_ECOLI [99] + + Cell division protein FtsQ L FTSQ_ECOLI [99] + +(no) Cell division protein FtsN L FTSN_ECOLI [99] + + DnaJ-like protein DjlA R DJLA_ECOLI [137] + + Protein ROT1 R, L ROT1_YEAST [138] - +(no) Syntaxin-1A R STX1A_HUMAN [102, 103, 105] + +(no) Syntaxin-2 L STX2_HUMAN [68] + + Vesicle-associated membrane protein 1 R VAMP1_HUMAN [68] + + Vesicle-associated membrane protein 4 L VAMP4_HUMAN [105] + +(no) Dysferlin L DYSF_HUMAN [111] + +(no) Melanocyte protein PMEL L PMEL_HUMAN [139] + + Sodium/potassium-transporting ATPase subunit gamma L PMEL_HUMAN [68, 140] + +(no) Cardiac phospholamban L PPLA_HUMAN [141, 142, 143] + +(no) Calcium-activated chloride channel regulator 2 L CLCA2_HUMAN [111] + +(no) Phospholipid scramblase 1 L PLS1_HUMAN [144] - +(no) V-type proton ATPase subunit S1 L VAS1_HUMAN [99] + +(no) ATP synthase subunit g, mitochondrial L ATP5L_HUMAN [145] + +(no) Transmembrane protein 132B L T132B_HUMAN [68] + +(no) Transcriptional activator CadC R CADC_ECOLI [146] - + Beta-1,4 N-acetylgalactosaminyltransferase 2 L B4GN2_HUMAN [111] + + UDP-glucuronosyltransferase 2B11 R UDB11_HUMAN [68] + + Diacylglycerol kinase epsilon L DGKE_HUMAN [147] + + Peptidoglycan synthase FtsI L FTSI_ECOLI [99] + +(no) Transmembrane protease serine 11D L TM11D_HUMAN [68] + + Furin L FURIN_HUMAN [68] + + Neuropathy target esterase R PLPL6_HUMAN [68] + + Patatin-like phospholipase domain-containing protein 7 R PLPL7_HUMAN [68] + + Sperm acrosome membrane-associated protein 1 R SACA1_HUMAN [68] + + Apoptosis regulator BAX L BAX_HUMAN [148] + + Chloride intracellular channel protein 1 L CLIC1_HUMAN [149, 150] + +(no) E3 ubiquitin-protein ligase RNF144B L R144B_HUMAN [68] + +(no) Ubiquitin-conjugating enzyme E2 J2 L, R UB2J2_HUMAN [111] + +(no) Protein FAM69A R FA69A_HUMAN [111] + + Protein FAM173B L F173B_HUMAN [99] + + Putative uncharacterized protein C8orf49 R CH049_HUMAN [68] + + Leucine-rich repeat and transmembrane domain-containing protein 2 L LRTM2_HUMAN [68] + + Protein ARMCX6 R ARMX6_HUMAN [68] + +

1"-" indicates no dimerization; “+(no)” indicates that model of a dimer was generated by TMDOCK, but not included in the Membranome database due to inconsistency with criteria for selection of functional structures. “w” indicates weak association based on TOXCAT data (for “Exp.” column) or on energy of association (for “Calc.” column).

Table 4. Bitopic proteins from Membranome with biologically relevant crystal structures of homodimers formed by water-soluble domains.
Family code Protein PDB code UniProt code Comment1 Receptor-type tyrosine-protein phosphatase O 2gjt PTPRO_HUMAN + * Receptor-type tyrosine-protein phosphatase N 2qt7 PTPRN_HUMAN + * IgE receptor, alpha chain 1rpq FCERA_HUMAN + Erythropoietin receptor 1ern EPOR_HUMAN + * Interleukin-6 receptor subunit beta 1bqu IL6RB_HUMAN + * Leptin receptor 3v6o LEPR_HUMAN + Cytokine receptor common subunit beta 1gh7 IL3RB_HUMAN + Interleukin-7 receptor subunit alpha 3up1 IL7RA_HUMAN + BTN3A1 ectodomain 4f9l BT3A1_HUMAN + Programmed cell death 1 ligand 1 3fn3 PD1L1_HUMAN + Leukocyte-associated Ig-like receptor 1 4esk LAIR1_HUMAN + Leukocyte immunoglobulin-like receptor A2 2otp LIRA2_HUMAN + Leukocyte immunoglobulin-like receptor B1 1vdg LIRB1_HUMAN + * Platelet glycoprotein VI 2gi7 GPVI_HUMAN +(no) Triggering receptor expressed on myeloid cells 1 1q8m TREM1_HUMAN + Natural cytotoxicity triggering receptor 3 3noi NCTR3_HUMAN + Basigin 3qqn BASI_HUMAN +(no) Glycoprotein cd8 alpha chain 2hp4 CD8A_HUMAN + CD2 antigen 1hng CD2_HUMAN + SLAM family member 5 2pkd SLAF5_HUMAN +(no) SLAM family member 6 2if7 SLAF6_HUMAN + Signal-regulatory protein gamma 4i2x SIRPG_HUMAN + Tyrosine-protein phosphatase non-receptor type substrate 1 2uv3 SHPS1_HUMAN + Netrin receptor UNC5B 1wmg UNC5B_HUMAN + CEAM1 4qxw CEAM1_HUMAN + * Cytotoxic T lymphocyte associated antigen 4 3osk CTLA4_HUMAN + * T-cell receptor beta-1 chain C region 2axh TRBC1_HUMAN + Myotonic dystrophy protein kinase 2vd5 DMPK_HUMAN + Mast/stem cell growth factor receptor Kit 2e9w KIT_HUMAN + * Ephrin type-b receptor 2 1b4f EPHB2_HUMAN + * Fibroblast growth factor receptor 1 1fgk FGFR1_HUMAN + * Fibroblast growth factor receptor 2 2psq FGFR2_HUMAN + * Insulin receptor 2hr7 INSR_HUMAN + * Tyrosine-protein kinase transmembrane receptor ROR2 3zzw ROR2_HUMAN +(no) * Hepatocyte growth factor receptor 3efj MET_HUMAN + * Proto-oncogene tyrosine-protein kinase receptor RET 2ivs RET_HUMAN + * Kinase/endoribonuclease 3p23 ERN1_HUMAN + * Serine/threonine-protein kinase/endoribonuclease IRE1 2rio IRE1_YEAST + Vascular endothelial growth factor receptor 1 4cl7 VGFR1_HUMAN + * Muscle, skeletal receptor tyrosine protein kinase 3hkl MUSK_HUMAN + * Hormone binding domain of the atrial natriuretic receptor 1dp4 ANPRA_HUMAN + * Macrophage receptor MARCO 2oya MARCO_HUMAN +(no) C-type lectin 2D 4qkh CLC2D_HUMAN + C-type lectin 4C 3wbp CLC4C_HUMAN + C-type lectin 4D 3whd CLC4D_HUMAN + * C-type lectin 4M 1k9j CLC4M_HUMAN + C-type lectin 7A 2bpd CLC7A_HUMAN + Early activation antigen cd69 3hup CD69_HUMAN + Immunoglobulin epsilon FC receptor 4gi0 FCER2_HUMAN + Killer cell lectin-like receptor subfamily G member 1 3ff9 KLRG1_HUMAN + Macrophage mannose receptor 1 1egg KLRG1_HUMAN + Oxidized low-density lipoprotein receptor 1 1ypq OLR1_HUMAN + Tumor necrosis factor receptor 1A 1ext TNR1A_HUMAN + Tumor necrosis factor receptor 11A 3me4 TNR11_HUMAN + Toll-like receptor 10 2j67 TLR10_HUMAN + * Toll-like receptor 2 1o77 TLR2_HUMAN Toll-like receptor 5 3j0a TLR5_HUMAN + * Toll-like receptor 6 4om7 TLR6_HUMAN + * Toll-like receptor 8 3w3n TLR8_HUMAN + * Plexin-A2 3al9 PLXA2_HUMAN + * Plexin-B1 2r2o PLXB1_HUMAN + * Plexin-C1 3kuz PLXC1_HUMAN + Syndecan-4 1ejp SDC4_HUMAN + * Neurogenic locus notch homolog protein 1 2he0 NOTC1_HUMAN + Amyloid-like protein 1 3pmr APLP1_HUMAN + T-cell antigen receptor alpha-beta complex 3of6 PTCRA_HUMAN +(no) CD44 antigen 4pz3 CD44_HUMAN + Ig mu chain C region 4jvu IGHM_HUMAN + B-cell antigen receptor 3kho CD79B_HUMAN + * Semaphorin-4D 1olz SEM4D_HUMAN + Semaphorin-6A 3okw SEM6A_HUMAN + Neuroligin-2 3bl8 NLGN2_HUMAN + Neuroligin-4 3be8 NLGNX_HUMAN + Seuroligin-1 3bix NLGN1_HUMAN + Fms-related tyrosine kinase 3 ligand 1ete FLT3L_HUMAN + KIT ligand 1scf SCF_HUMAN + * Fibronectin type III domain-containing protein 5 4lsd FNDC5_HUMAN +(no) Macrophage colony-stimulating factor 1 4fa8 CSF1_HUMAN + Fractalkine 1f2l X3CL1_HUMAN +(no) Modulator protein MzrA 4pwu MZRA_ECOLI + Coxsackie virus and adenovirus receptor 1eaj CXAR_HUMAN + * Junctional adhesion molecule A 1nbq JAM1_HUMAN + Kin of IRRE-like protein 1 4ofd KIRR1_HUMAN + Amphoterin-induced protein 2xot AMGO1_HUMAN + Cell adhesion molecule 2 3m45 CADM2_HUMAN + * Cell adhesion molecule 3 1z9m CADM3_HUMAN + * Cytotoxic and regulatory T-cell molecule 3rbg CRTAM_HUMAN + Poliovirus receptor-related protein 1 3alp PVRL1_HUMAN + Poliovirus receptor-related protein 2 4hza PVRL2_HUMAN + Poliovirus receptor-related protein 4 4frw PVRL4_HUMAN + Neural cell adhesion molecule 1 2vkw NCAM1_HUMAN + Vascular cell adhesion protein 1 1vsc VCAM1_HUMAN + Cadherin-11 2a4c CAD11_HUMAN + Cadherin-1 3q2v CADH1_HUMAN + * Cadherin-20 1zvn CAD20_HUMAN + Cadherin-2 4nup CADH2_HUMAN + Cadherin-3 4nqq CADH3_HUMAN + * Cadherin-5 3ppe CADH5_HUMAN + Cadherin-6 3lnd CADH6_HUMAN + Cadherin-8 1zxk CADH8_HUMAN + Bone marrow stromal antigen 2 ectodomain 2xg7 BST2_HUMAN + * P-selectin 1g1q LYAM3_HUMAN + * Zona pellucida sperm-binding protein 3 3ef7 ZP3_HUMAN + Motility protein B 2zvy MOTB_ECOLI +(no) Cell shape-determining protein MreC 2j5u MREC_ECOLI + Chloroplast translocase 34 3bb1 TOC34_ARATH +(no) Signal recognition particle receptor subunit beta 2ged SRPB_YEAST + Cation-dependent mannose-6-phosphate receptor 2rl8 MPRD_HUMAN + Complement decay-accelerating factor 1ojv MPRD_HUMAN + Cation-independent mannose-6-phosphate receptor 1syo MPRI_HUMAN + Mitochondrial import receptor subunit TOM70 2gw1 TOM70_YEAST + Mitochondrial dynamic protein MID51 4nxt MID51_HUMAN + Putative type II secretion system protein M 1uv7 GSPM_ECOLI + Putative type II secretion system protein G 3fu1 GSPG_ECOLI + t-SNARE affecting a late Golgi compartment protein 1 2c5j TLG1_YEAST +(no) Extended synaptotagmin-2 4p42 ESYT2_HUMAN + Stromal interaction molecule 1 2maj STML1_HUMAN + Calcium uptake protein 1, mitochondrial 4nsd MICU1_HUMAN + Periplasmic domain of TOLR 2jwk TOLR_ECOLI +(no) Lipopolysaccharide export protein LptC 4b54 LPTC_ECOLI + Zinc finger cdgsh-type domain 1 2qh7 CISD1_HUMAN + Fatty aldehyde dehydrogenase 4qgk AL3A2_HUMAN +(no) Mitochondrial Erv2 protein 1jr8 ERV2_YEAST + Sulfhydryl oxidase 1 4p2l QSOX1_HUMAN +(no) Primary amine oxidase 2y73 AOC3_HUMAN + Zinc finger cdgsh-type domain 2 3fnv CISD2_HUMAN +(no) Formate-dependent nitrite reductase subunit NrfG 2e2e NRFG_ECOLI + Polypeptide N-acetylgalactosaminyltransferase 2 4d0t GALT2_HUMAN + N-acetyllactosaminide alpha-1,3-galactosyltransferase 2vfz GGTA1_HUMAN + 3-beta-glucuronosyltransferase 1 1v82 B3GA1_HUMAN + 3-beta-glucuronosyltransferase 2 2d0j B3GA2_HUMAN + 3-beta-glucuronosyltransferase 3 1fgg B3GA3_HUMAN + Beta-1,4-galactosyltransferase 7 4irp B4GT7_HUMAN + UDP-glucuronosyltransferase 2B7 2o6l UD2B7_HUMAN +(no) Beta-1,6-N-acetylglucosaminyltransferase 2gak GCNT1_HUMAN + Catechol o-methyltransferase 4pyq COMT_HUMAN +(no) Catechol o-methyltransferase 2avd CMTD1_HUMAN + Protein-tyrosine sulfotransferase 2 3ap1 TPST2_HUMAN + Adenosine monophosphatase-protein transferase 4u04 FICD_HUMAN + Hexokinase-2 2nzt HXK2_ARATH + Leucyl-cystinyl aminopeptidase 4p8q LCAP_HUMAN + Meprin A subunit beta 4gwm MEP1B_HUMAN + Glutamate carboxypeptidase 2 1z8l FOLH1_HUMAN + Transferrin receptor protein 1 1cx8 TFR1_HUMAN + Dipeptidyl aminopeptidase X. 1xfd DPP6_HUMAN + Dipeptidyl peptidase IV 2qt9 DPP4_HUMAN + * Seprase 1z68 SEPR_HUMAN + Prostatic acid phosphatase 1nd5 PPAP_HUMAN + Ectonucleotide pyrophosphatase/phosphodiesterase 4b56 ENPP1_HUMAN + Calcium-activated nucleotidase 2h2n CANT1_HUMAN +(no) Fatty acid amide hydrolase 1mt5 FAAH1_HUMAN + Bak domain 4u2u BAK_HUMAN + Bcl-2-like protein 1 3inq B2CL1_HUMAN + Bcl-2-like protein 2 2y6w B2CL2_HUMAN + Carbonic anhydrase 12 1jcz CAH12_HUMAN + Carbonic anhydrase 9 3iai CAH9_HUMAN + UDP-glucuronic acid decarboxylase 1 4gll UXS1_HUMAN + Sphingosine-1-phosphate lyase 1 4q6r SGPL1_HUMAN +(no) Prostaglandin E synthase 2 1z9h PGES2_HUMAN + Chloride intracellular channel protein 1 1rk4 CLIC1_HUMAN +(no) * E3 ubiquitin-protein ligase ZNRF3 4c86 ZNRF3_HUMAN +

1 See footnotes for Table 3. “*” indicates that the same protein was already included in Tables 1-3, i.e. its TM domains were experimentally shown to form homodimers. Only one, representative PDB model was included for each dimer.

Table 5. Bitopic proteins from Membranome that form homodimers according to UniProt annotation.
Family code Protein UniProt code Comment1 Receptor-type tyrosine-protein phosphatase gamma PTPRG_HUMAN + * Receptor-type tyrosine-protein phosphatase H PTPRH_HUMAN + * Receptor-type tyrosine-protein phosphatase epsilon PTPRE_HUMAN + * Erythropoietin receptor EPOR_HUMAN + * Growth hormone receptor GHR_HUMAN + Prolactin receptor PRLR_HUMAN + * Thrombopoietin receptor TPOR_HUMAN + * Granulocyte colony-stimulating factor receptor CSF3R_HUMAN + Interleukin-6 receptor subunit beta IL6RB_HUMAN + * Leptin receptor LEPR_HUMAN + Interleukin-1 receptor accessory protein-like 1 IRPL1_HUMAN + Butyrophilin subfamily 3 member A1 BT3A1_HUMAN + Butyrophilin subfamily 3 member A2 BT3A2_HUMAN +(no) Butyrophilin subfamily 3 member A3 BT3A3_HUMAN + Leukocyte immunoglobulin-like receptor subfamily A member 2 LIRA2_HUMAN + Myelin-oligodendrocyte glycoprotein MOG_HUMAN +(no) Roundabout homolog 1 ROBO1_HUMAN + Natural cytotoxicity triggering receptor 3 NCTR3_HUMAN + T-cell surface glycoprotein CD8 alpha chain CD8A_HUMAN + SLAM family member 5 SLAF5_HUMAN +(no) SLAM family member 6 SLAF6_HUMAN + T-cell-specific surface glycoprotein CD28 CD28_HUMAN + Lymphocyte antigen 6 complex locus protein G6f LY66F_HUMAN + Advanced glycosylation end product-specific receptor RAGE_HUMAN + Signal-regulatory protein beta-1 SIRB1_HUMAN + T-cell immunoreceptor with Ig and ITIM domains TIGIT_HUMAN + Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 1 LRIT1_HUMAN +(no) Interleukin-15 receptor subunit alpha I15RA_HUMAN + T-lymphocyte activation antigen CD86 CD86_HUMAN + Cytotoxic T-lymphocyte protein 4 CTLA4_HUMAN + * Inducible T-cell costimulator ICOS_HUMAN + Myotonin-protein kinase DMPK_HUMAN + TGF-beta receptor type-1 TGFR1_HUMAN + TGF-beta receptor type-2 TGFR2_HUMAN - Beta-type platelet-derived growth factor receptor PGFRB_HUMAN + * Mast/stem cell growth factor receptor Kit KIT_HUMAN + * Platelet-derived growth factor receptor alpha PGFRA_HUMAN + * Receptor-type tyrosine-protein kinase FLT3 FLT3_HUMAN + * Vascular endothelial growth factor receptor 1 VGFR1_HUMAN + * Vascular endothelial growth factor receptor 2 VGFR2_HUMAN + * Vascular endothelial growth factor receptor 3 VGFR3_HUMAN + * Epidermal growth factor receptor EGFR_HUMAN + * Receptor tyrosine-protein kinase erbB-2 ERBB2_HUMAN + * Receptor tyrosine-protein kinase erbB-3 ERBB3_HUMAN + * Receptor tyrosine-protein kinase erbB-4 ERBB4_HUMAN + * Ephrin type-A receptor 1 EPHA1_HUMAN + * Fibroblast growth factor receptor 1 FGFR1_HUMAN + * Fibroblast growth factor receptor 2 FGFR2_HUMAN + * Fibroblast growth factor receptor 3 FGFR3_HUMAN + * Fibroblast growth factor receptor 4 FGFR4_HUMAN + * ALK tyrosine kinase receptor ALK_HUMAN + * BDNF/NT-3 growth factors receptor NTRK2_HUMAN + * Epithelial discoidin domain-containing receptor 1 DDR1_HUMAN + * High affinity nerve growth factor receptor NTRK1_HUMAN + * Leukocyte tyrosine kinase receptor LTK_HUMAN + * Tyrosine-protein kinase transmembrane receptor ROR2 ROR2_HUMAN +(no) * Angiopoietin-1 receptor TIE2_HUMAN + * Tyrosine-protein kinase receptor TYRO3 TYRO3_HUMAN + * AarF domain-containing protein kinase 4 ADCK4_HUMAN + * Atypical kinase ADCK3, mitochondrial ADCK3_HUMAN + * LRR receptor-like serine/threonine-protein kinase ERECTA ERECT_ARATH + LRR receptor-like serine/threonine-protein kinase ERL1 ERL1_ARATH + LRR receptor-like serine/threonine-protein kinase FLS2 FLS2_ARATH + Protein BRASSINOSTEROID INSENSITIVE 1 BRI1_ARATH + Somatic embryogenesis receptor kinase 1 SERK1_ARATH + Somatic embryogenesis receptor kinase 2 SERK2_ARATH + Serine/threonine-protein kinase/endoribonuclease IRE1a IRE1A_ARATH + Serine/threonine-protein kinase/endoribonuclease IRE1 ERN1_HUMAN + * Serine/threonine-protein kinase/endoribonuclease IRE1 IRE1_YEAST + Putative serine/threonine-protein kinase-like protein CCR3 ACCR3_ARATH + Serine/threonine-protein kinase-like protein ACR4 ACR4L_ARATH + * Serine/threonine-protein kinase-like protein CCR1 ACCR1_ARATH + Serine/threonine-protein kinase-like protein CCR2 ACCR2_ARATH + Serine/threonine-protein kinase-like protein CCR4 ACCR4_ARATH + Chitin elicitor receptor kinase 1 CERK1_ARATH + Muscle, skeletal receptor tyrosine protein kinase MUSK_HUMAN + * Atrial natriuretic peptide receptor 3 ANPRC_HUMAN + Atrial natriuretic peptide receptor A ANPRA_HUMAN + * B-cell differentiation antigen CD72 CD72_HUMAN + C-type lectin domain family 12 member B CL12B_HUMAN + C-type lectin domain family 1 member B CLC1B_HUMAN + C-type lectin domain family 2 member A CLC2A_HUMAN + C-type lectin domain family 2 member D CLC2D_HUMAN + C-type lectin domain family 4 member E CLC4E_HUMAN + C-type lectin domain family 5 member A CLC5A_HUMAN + C-type lectin domain family 7 member A CLC7A_HUMAN + C-type lectin domain family 9 member A CLC9A_HUMAN + Early activation antigen CD69 CD69_HUMAN + Killer cell lectin-like receptor subfamily B member 1 KLRB1_HUMAN + Killer cell lectin-like receptor subfamily F member 1 KLRF1_HUMAN + Killer cell lectin-like receptor subfamily F member 2 KLRF2_HUMAN + Killer cell lectin-like receptor subfamily G member 1 KLRG1_HUMAN + NKG2-D type II integral membrane protein NKG2D_HUMAN + Oxidized low-density lipoprotein receptor 1 OLR1_HUMAN + Low-density lipoprotein receptor-related protein 5 LRP5_HUMAN + Low-density lipoprotein receptor-related protein 6 LRP6_HUMAN + Tumor necrosis factor receptor superfamily member 3 TNR3_HUMAN + Tumor necrosis factor receptor superfamily member 5 TNR5_HUMAN + Tumor necrosis factor receptor superfamily member 10B TR10B_HUMAN + Tumor necrosis factor receptor superfamily member 16 TNR16_HUMAN + * Tumor necrosis factor receptor superfamily member 25 TNR25_HUMAN + CD27 antigen CD27_HUMAN + Toll-like receptor 10 TLR10_HUMAN + * Toll-like receptor 3 TLR3_HUMAN + * Toll-like receptor 4 TLR4_HUMAN + * Toll-like receptor 5 TLR5_HUMAN + * Toll-like receptor 8 TLR8_HUMAN + * Interleukin-17 receptor D I17RD_HUMAN + T-cell surface glycoprotein CD3 zeta chain CD3Z_HUMAN + * Integrin alpha-4 ITA4_HUMAN + * Integrin beta-1 ITB1_HUMAN +(no) * Neuropilin-1 NRP1_HUMAN + * Plexin-A2 PLXA2_HUMAN + * Plexin-B3 PLXB3_HUMAN + Plexin-C1 PLXC1_HUMAN + Syndecan-4 SDC4_HUMAN + * Sialomucin core protein 24 MUC24_HUMAN + Amyloid beta A4 protein A4_HUMAN + * Amyloid-like protein 1 APLP1_HUMAN + Lymphatic vessel endothelial hyaluronic acid receptor 1 LYVE1_HUMAN + HLA class I histocompatibility antigen, alpha chain G HLAG_HUMAN + T-lymphocyte activation antigen CD80 CD80_HUMAN +(no) Semaphorin-4D SEM4D_HUMAN + Semaphorin-6A SEM6A_HUMAN + Neuroligin-3 NLGN3_HUMAN + Neuroligin-4, X-linked NLGNX_HUMAN + Neuroligin-4, Y-linked NLGNY_HUMAN + Fms-related tyrosine kinase 3 ligand FLT3L_HUMAN + Kit ligand SCF_HUMAN + * Tumor necrosis factor ligand superfamily member 18 TNF18_HUMAN +(no) Protein APCDD1 APCD1_HUMAN + Macrophage colony-stimulating factor 1 CSF1_HUMAN + TYRO protein tyrosine kinase-binding protein TYOBP_HUMAN + * LINGO-1 protein LIGO1_HUMAN + Hematopoietic cell signal transducer HCST_HUMAN + Melanocortin-2 receptor accessory protein 2 MRAP2_HUMAN + Melanocortin-2 receptor accessory protein MRAP_HUMAN + Signaling threshold-regulating transmembrane adapter 1 SIT1_HUMAN + T-cell receptor-associated transmembrane adapter 1 TRAT1_HUMAN + Coxsackievirus and adenovirus receptor CXAR_HUMAN + * Hepatocyte cell adhesion molecule HECAM_HUMAN + Junctional adhesion molecule-like JAML1_HUMAN + Myelin protein P0 MYP0_HUMAN + * Neurofascin NFASC_HUMAN + Kin of IRRE-like protein 1 KIRR1_HUMAN + Amphoterin-induced protein 1 AMGO1_HUMAN + Intercellular adhesion molecule 1 ICAM1_HUMAN + Cell adhesion molecule 1 CADM1_HUMAN + Cell adhesion molecule 2 CADM2_HUMAN + * Cell adhesion molecule 3 CADM3_HUMAN + * Cell adhesion molecule 4 CADM4_HUMAN + Poliovirus receptor-related protein 1 PVRL1_HUMAN + Poliovirus receptor-related protein 3 PVRL3_HUMAN + T-cell surface protein tactile TACT_HUMAN + Mucosal addressin cell adhesion molecule 1 MADCA_HUMAN + Mucin-13 MUC13_HUMAN + Cadherin-1 CADH1_HUMAN + * Protocadherin Fat 2 FAT2_HUMAN + Glycophorin-A GLPA_HUMAN + * Bone marrow stromal antigen 2 BST2_HUMAN + * Teneurin-1 TEN1_HUMAN + Teneurin-2 TEN2_HUMAN + Teneurin-3 TEN3_HUMAN + Teneurin-4 TEN4_HUMAN + P-selectin glycoprotein ligand 1 SELPL_HUMAN + Sarcolemmal membrane-associated protein SLMAP_HUMAN + Podocalyxin-like protein 2 PDXL2_HUMAN + Izumo sperm-egg fusion protein 1 IZUM1_HUMAN + Izumo sperm-egg fusion protein 3 IZUM3_HUMAN + Endoglin EGLN_HUMAN + Zona pellucida sperm-binding protein 1 ZP1_HUMAN + Zona pellucida sperm-binding protein 2 ZP2_HUMAN + Zona pellucida sperm-binding protein 3 ZP3_HUMAN + Collagen alpha-1(XXV) chain COPA1_HUMAN + SUN domain-containing protein 1 SUN1_DICDI - WPP domain-interacting protein 1 WIP1_ARATH + WPP domain-interacting protein 2 WIP2_ARATH + WPP domain-interacting tail-anchored protein 1 WIT1_ARATH +(no) Cell division protein FtsL FTSL_ECOLI + * Cell shape-determining protein MreC MREC_ECOLI + Mitochondrial import inner membrane translocase subunit TIM14 TIM14_YEAST + DnaJ-like protein DjlA DJLA_ECOLI + * Translocase of chloroplast 120, chloroplastic TC120_ARATH +(no) Translocase of chloroplast 132, chloroplastic TC132_ARATH + Translocase of chloroplast 159, chloroplastic TC159_ARATH + Translocase of chloroplast 90, chloroplastic TOC90_ARATH +(no) Translocase of chloroplast 34, chloroplastic TOC34_ARATH +(no) Leucine-rich repeat-containing protein 59 LRC59_HUMAN + Protein RIC-3 RIC3_HUMAN +(no) Cation-dependent mannose-6-phosphate receptor MPRD_HUMAN + Integral membrane protein 2B ITM2B_HUMAN + Stomatin-like protein 3 STML3_HUMAN +(no) Protein SCO1 homolog, mitochondrial SCO1_HUMAN + ATPase family AAA domain-containing protein 3A ATD3A_HUMAN +(no) BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 BNIP3_HUMAN + * BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like BNI3L_HUMAN + Mitochondrial dynamic protein MID51 MID51_HUMAN + Synaptotagmin-10 SYT10_HUMAN + Synaptotagmin-11 SYT11_HUMAN +(no) Synaptotagmin-12 SYT12_HUMAN +(no) Synaptotagmin-14 SYT14_HUMAN + Synaptotagmin-15 SYT15_HUMAN + Synaptotagmin-3 SYT3_HUMAN +(no) Synaptotagmin-5 SYT5_HUMAN + Synaptotagmin-6 SYT6_HUMAN + Synaptotagmin-8 SYT8_HUMAN +(no) Extended synaptotagmin-2 ESYT2_HUMAN + Transmembrane emp24 domain-containing protein 10 TMEDA_HUMAN + Transmembrane emp24 domain-containing protein 1 TMED1_HUMAN + Transmembrane emp24 domain-containing protein 2 TMED2_HUMAN + Transmembrane emp24 domain-containing protein 7 TMED7_HUMAN +(no) Transmembrane emp24 domain-containing protein 9 TMED9_HUMAN + Golgin subfamily A member 5 GOGA5_HUMAN + Golgin subfamily B member 1 GOGB1_HUMAN + Protein CASP CASP_HUMAN + Vesicle-associated membrane protein-associated protein A VAPA_HUMAN + Vesicle-associated membrane protein-associated protein B/C VAPB_HUMAN + Vesicle-associated protein 1-1 VAP11_ARATH + Kinectin KTN1_HUMAN + Plasmalemma vesicle-associated protein PLVAP_HUMAN + Dyslexia-associated protein KIAA0319 K0319_HUMAN + Mitochondrial fission factor MFF_HUMAN + Plasma membrane ATPase proteolipid 1 PMP1_YEAST + Plasma membrane ATPase proteolipid 2 PMP2_YEAST + Multidrug resistance protein A EMRA_ECOLI + Lipopolysaccharide export system protein LptC LPTC_ECOLI + Cyclic AMP-responsive element-binding protein 3 CREB3_HUMAN + Cyclic AMP-responsive element-binding protein 3-like protein 3 CR3l3_HUMAN + bZIP transcription factor 28 BZP28_ARATH + Cyclic AMP-dependent transcription factor ATF-6 alpha ATF6A_HUMAN + Cyclic AMP-dependent transcription factor ATF-6 beta ATF6B_HUMAN + Amine oxidase [flavin-containing] A AOFA_HUMAN + Amine oxidase [flavin-containing] B AOFB_HUMAN + CDGSH iron-sulfur domain-containing protein 1 CISD1_HUMAN + CDGSH iron-sulfur domain-containing protein 2 CISD2_HUMAN +(no) Vitamin D 25-hydroxylase CP2R1_HUMAN +(no) Corticosteroid 11-beta-dehydrogenase isozyme 1 DHI1_HUMAN + Aldehyde dehydrogenase family 3 member I1, chloroplastic AL3I1_ARATH + FAD-linked sulfhydryl oxidase ERV2 ERV2_YEAST + Type III iodothyronine deiodinase IOD3_HUMAN + Transmembrane prolyl 4-hydroxylase P4HTM_HUMAN + Membrane primary amine oxidase AOC3_HUMAN + Beta-1,4 N-acetylgalactosaminyltransferase 1 B4GN1_HUMAN + Xyloside xylosyltransferase 1 XXLT1_HUMAN Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 B3GA1_HUMAN + Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 B3GA2_HUMAN + Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3 B3GA3_HUMAN + Beta-1,4-galactosyltransferase 1 B4GT1_HUMAN + Glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1 C1GLT_HUMAN + Chitobiosyldiphosphodolichol beta-mannosyltransferase ALG1_YEAST + Probable arabinosyltransferase ARAD1 ARAD1_ARATH +(no) Probable arabinosyltransferase ARAD2 ARAD2_ARATH + Fukutin-related protein FKRP_HUMAN + Catechol O-methyltransferase domain-containing protein 1 CMTD1_HUMAN + Carbohydrate sulfotransferase 15 CHSTF_HUMAN + Carbohydrate sulfotransferase 2 CHST2_HUMAN + Protein-tyrosine sulfotransferase 2 TPST2_HUMAN + Penicillin-binding protein 1B PBPB_ECOLI + Retroviral-like aspartic protease 1 APRV1_HUMAN + Aminopeptidase N AMPN_HUMAN + Aminopeptidase Q AMPQ_HUMAN + Glutamyl aminopeptidase AMPE_HUMAN + Leucyl-cystinyl aminopeptidase LCAP_HUMAN + Thyrotropin-releasing hormone-degrading ectoenzyme TRHDE_HUMAN + Collectrin TMM27_HUMAN +(no) Meprin A subunit alpha MEP1A_HUMAN + Endothelin-converting enzyme 1 ECE1_HUMAN + Glutamate carboxypeptidase 2 FOLH1_HUMAN + N-acetylated-alpha-linked acidic dipeptidase 2 NALD2_HUMAN + Transferrin receptor protein 1 TFR1_HUMAN + Transferrin receptor protein 2 TFR2_HUMAN + Dipeptidyl aminopeptidase-like protein 6 DPP6_HUMAN + Dipeptidyl peptidase 4 DPP4_HUMAN + * Seprase SEPR_HUMAN + Mitochondrial cardiolipin hydrolase PLD6_HUMAN + Prostatic acid phosphatase, isoform 2 PPAP_HUMAN + Testicular acid phosphatase PPAT_HUMAN + Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 ENPP1_HUMAN + Guanosine-diphosphatase GDA1_YEAST + N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase NAGPA_HUMAN + Klotho KLOT_HUMAN + Alpha-mannosidase 2 GMAN2_ARATH + Alpha-mannosidase 2 MA2A1_HUMAN + Alpha-mannosidase 2x MA2A2_HUMAN +(no) Fatty-acid amide hydrolase 1 FAAH1_HUMAN + Fatty-acid amide hydrolase 2 FAAH2_HUMAN +(no) Probable inactive purple acid phosphatase 2 PPA2_ARATH + Probable inactive purple acid phosphatase 9 PPA9_ARATH + AMP deaminase AMPD_ARATH + Complement decay-accelerating factor DAF_HUMAN + Apoptosis regulator BAX BAX_HUMAN + * Apoptosis regulator Bcl-2 BCL2_HUMAN +(no) Bcl-2 homologous antagonist/killer BAK_HUMAN + Bcl-2-like protein 1 B2CL1_HUMAN + Receptor-binding cancer antigen expressed on SiSo cells RCAS1_HUMAN +(no) Carbonic anhydrase 12 CAH12_HUMAN + UDP-glucuronic acid decarboxylase 2 UXS2_ARATH + Sphingosine-1-phosphate lyase 1 SGPL1_HUMAN +(no) Prostaglandin E synthase 2 PGES2_HUMAN + Chloride intracellular channel protein 1 CLIC1_HUMAN +(no) * Peptidyl-prolyl cis-trans isomerase D PPID_ECOLI + Long-chain fatty acid transport protein 1 S27A1_HUMAN + Cell cycle exit and neuronal differentiation protein 1 CEND_HUMAN +

See footnotes for Table 4.

  1. Lomize AL, Pogozheva ID. TMDOCK: an energy-based method for modeling alpha-helical dimers in membranes. J Mol Biol. 2017;429(3):390-8. doi: 10.1016/j.jmb.2016.09.005. PubMed PMID: 27622289.
  2. Finger C, Escher C, Schneider D. The single transmembrane domains of human receptor tyrosine kinases encode self-interactions. Sci Signal. 2009;2(89):ra56. doi: 10.1126/scisignal.2000547. PubMed PMID: 19797273.
  3. Muhle-Goll C, Hoffmann S, Afonin S, Grage SL, Polyansky AA, Windisch D, Zeitler M, Burck J, Ulrich AS. Hydrophobic matching controls the tilt and stability of the dimeric platelet-derived growth factor receptor (PDGFR) beta transmembrane segment. J Biol Chem. 2012;287(31):26178-86. doi: 10.1074/jbc.M111.325555. PubMed PMID: 22619173.
  4. Oates J, King G, Dixon AM. Strong oligomerization behavior of PDGFbeta receptor transmembrane domain and its regulation by the juxtamembrane regions. Biochim Biophys Acta. 2010;1798(3):605-15. doi: 10.1016/j.bbamem.2009.12.016. PubMed PMID: 20036637.
  5. Windisch D, Hoffmann S, Afonin S, Vollmer S, Benamira S, Langer B, Burck J, Muhle-Goll C, Ulrich AS. Structural role of the conserved cysteines in the dimerization of the viral transmembrane oncoprotein E5. Biophys J. 2010;99(6):1764-72. doi: 10.1016/j.bpj.2010.06.073. PubMed PMID: 20858420.
  6. Bocharov EV, Lesovoy DM, Pavlov KV, Pustovalova YE, Bocharova OV, Arseniev AS. Alternative packing of EGFR transmembrane domain suggests that protein-lipid interactions underlie signal conduction across membrane. Biochim Biophys Acta. 2016;1858(6):1254-61. doi: 10.1016/j.bbamem.2016.02.023. PubMed PMID: 26903218.
  7. Endres NF, Das R, Smith AW, Arkhipov A, Kovacs E, Huang Y, Pelton JG, Shan Y, Shaw DE, Wemmer DE, Groves JT, Kuriyan J. Conformational coupling across the plasma membrane in activation of the EGF receptor. Cell. 2013;152(3):543-56. doi: 10.1016/j.cell.2012.12.032. PubMed PMID: 23374349.
  8. Escher C, Cymer F, Schneider D. Two GxxxG-like motifs facilitate promiscuous interactions of the human ErbB transmembrane domains. J Mol Biol. 2009;389(1):10-6. doi: 10.1016/j.jmb.2009.04.002. PubMed PMID: 19361517.
  9. Mendrola JM, Berger MB, King MC, Lemmon MA. The single transmembrane domains of ErbB receptors self-associate in cell membranes. J Biol Chem. 2002;277(7):4704-12. doi: 10.1074/jbc.M108681200. PubMed PMID: 11741943.
  10. Duneau JP, Vegh AP, Sturgis JN. A dimerization hierarchy in the transmembrane domains of the HER receptor family. Biochemistry. 2007;46(7):2010-9. doi: 10.1021/bi061436f. PubMed PMID: 17253768.
  11. Placone J, He L, Del Piccolo N, Hristova K. Strong dimerization of wild-type ErbB2/Neu transmembrane domain and the oncogenic Val664Glu mutant in mammalian plasma membranes. Biochim Biophys Acta. 2014;1838(9):2326-30. doi: 10.1016/j.bbamem.2014.03.001. PubMed PMID: 24631664.
  12. Sawma P, Roth L, Blanchard C, Bagnard D, Cremel G, Bouveret E, Duneau JP, Sturgis JN, Hubert P. Evidence for new homotypic and heterotypic interactions between transmembrane helices of proteins involved in receptor tyrosine kinase and neuropilin signaling. J Mol Biol. 2014;426(24):4099-111. doi: 10.1016/j.jmb.2014.10.007. PubMed PMID: 25315821.
  13. Stanley AM, Fleming KG. The transmembrane domains of ErbB receptors do not dimerize strongly in micelles. J Mol Biol. 2005;347(4):759-72. doi: 10.1016/j.jmb.2005.01.059. PubMed PMID: 15769468.
  14. Bocharov EV, Mineev KS, Volynsky PE, Ermolyuk YS, Tkach EN, Sobol AG, Chupin VV, Kirpichnikov MP, Efremov RG, Arseniev AS. Spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 presumably corresponding to the receptor active state. Journal of Biological Chemistry. 2008;283(11):6950-6. doi: 10.1074/jbc.M709202200. PubMed PMID: 18178548.
  15. Bragin PE, Mineev KS, Bocharova OV, Volynsky PE, Bocharov EV, Arseniev AS. HER2 Transmembrane Domain Dimerization Coupled with Self-Association of Membrane-Embedded Cytoplasmic Juxtamembrane Regions. J Mol Biol. 2016;428(1):52-61. doi: 10.1016/j.jmb.2015.11.007. PubMed PMID: 26585403.
  16. Bocharov EV, Mineev KS, Volynsky PE, Ermolyuk YS, Tkach EN, Sobol AG, Chupin VV, Kirpichnikov MP, Efremov RG, Arseniev AS. Spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 presumably corresponding to the receptor active state. J Biol Chem.
  17. Gerber D, Sal-Man N, Shai Y. Two motifs within a transmembrane domain, one for homodimerization and the other for heterodimerization. J Biol Chem. 2004;279(20):21177-82. doi: 10.1074/jbc.M400847200. PubMed PMID: 14985340.
  18. Brennan PJ, Kumagai T, Berezov A, Murali R, Greene MI. HER2/Neu: mechanisms of dimerization/oligomerization. Oncogene. 2002;21(2):328. doi: 10.1038/sj.onc.1205119. PubMed PMID: 11840330.
  19. Bennasroune A, Gardin A, Auzan C, Clauser E, Dirrig-Grosch S, Meira M, Appert-Collin A, Aunis D, Cremel G, Hubert P. Inhibition by transmembrane peptides of chimeric insulin receptors. Cell Mol Life Sci : CMLS. 2005;62(18):2124-31. doi: 10.1007/s00018-005-5226-9. PubMed PMID: 16132228.
  20. Beevers AJ, Damianoglou A, Oates J, Rodger A, Dixon AM. Sequence-dependent oligomerization of the Neu transmembrane domain suggests inhibition of "conformational switching" by an oncogenic mutant. Biochemistry. 2010;49(13):2811-20. doi: 10.1021/bi902087v. PubMed PMID: 20180588.
  21. Mineev KS, Khabibullina NF, Lyukmanova EN, Dolgikh DA, Kirpichnikov MP, Arseniev AS. Spatial structure and dimer--monomer equilibrium of the ErbB3 transmembrane domain in DPC micelles. Biochim Biophys Acta. 2011;1808(8):2081-8. doi: 10.1016/j.bbamem.2011.04.017. PubMed PMID: 21575594.
  22. Bocharov EV, Mayzel ML, Volynsky PE, Goncharuk MV, Ermolyuk YS, Schulga AA, Artemenko EO, Efremov RG, Arseniev AS. Spatial Structure and pH-dependent Conformational Diversity of Dimeric Transmembrane Domain of the Receptor Tyrosine Kinase EphA1. Journal of Biological Chemistry. 2008;283(43):29385-95. doi: 10.1074/jbc.M803089200. PubMed PMID: 18728013.
  23. Bocharov EV, Mayzel ML, Volynsky PE, Mineev KS, Tkach EN, Ermolyuk YS, Schulga AA, Efremov RG, Arseniev AS. Left-handed dimer of EphA2 transmembrane domain: helix packing diversity among receptor tyrosine kinases. Biophysical Journal. 2010;98(5):881-9. doi: 10.1016/j.bpj.2009.11.008. PubMed PMID: 18728013.
  24. Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet. 1995;11(4):462-4. doi: 10.1038/ng1295-462. PubMed PMID: 7493034.
  25. Bonaventure J, Rousseau F, Legeai-Mallet L, Le Merrer M, Munnich A, Maroteaux P. Common mutations in the gene encoding fibroblast growth factor receptor 3 account for achondroplasia, hypochondroplasia and thanatophoric dysplasia. Acta Paediatr Suppl. 1996;417:33-8. PubMed PMID: 9055906.
  26. Webster MK, Donoghue DJ. FGFR activation in skeletal disorders: too much of a good thing. Trends Genet. 1997;13(5):178-82. PubMed PMID: 9154000.
  27. Bocharov EV, Lesovoy DM, Goncharuk SA, Goncharuk MV, Hristova K, Arseniev AS. Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies. Structure. 2013;21(11):2087-93. doi: 10.1016/j.str.2013.08.026. PubMed PMID: 24120763.
  28. Manni S, Mineev KS, Usmanova D, Lyukmanova EN, Shulepko MA, Kirpichnikov MP, Winter J, Matkovic M, Deupi X, Arseniev AS, Ballmer-Hofer K. Structural and functional characterization of alternative transmembrane domain conformations in VEGF receptor 2 activation. Structure. 2014;22(8):1077-89. doi: 10.1016/j.str.2014.05.010. PubMed PMID: 24980797.
  29. Maruyama IN. Activation of transmembrane cell-surface receptors via a common mechanism? The "rotation model". Bioessays. 2015;37(9):959-67. doi: 10.1002/bies.201500041. PubMed PMID: 26241732.
  30. Vilar M, Charalampopoulos I, Kenchappa RS, Simi A, Karaca E, Reversi A, Choi S, Bothwell M, Mingarro I, Friedman WJ, Schiavo G, Bastiaens PI, Verveer PJ, Carter BD, Ibanez CF. Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers. Neuron. 2009;62(1):72-83. doi: 10.1016/j.neuron.2009.02.020. PubMed PMID: 19376068.
  31. Mineev KS, Goncharuk SA, Kuzmichev PK, Vilar M, Arseniev AS. NMR Dynamics of Transmembrane and Intracellular Domains of p75NTR in Lipid-Protein Nanodiscs. Biophys J. 2015;109(4):772-82. doi: 10.1016/j.bpj.2015.07.009. PubMed PMID: 26287629.
  32. Godfroy JI, 3rd, Roostan M, Moroz YS, Korendovych IV, Yin H. Isolated Toll-like receptor transmembrane domains are capable of oligomerization. PLoS One. 2012;7(11):e48875. doi: 10.1371/journal.pone.0048875. PubMed PMID: 23155421.
  33. Mineev KS, Goncharuk SA, Arseniev AS. Toll-like receptor 3 transmembrane domain is able to perform various homotypic interactions: an NMR structural study. FEBS Lett. 2014;588(21):3802-7. doi: 10.1016/j.febslet.2014.08.031. PubMed PMID: 25217833.
  34. Call ME, Schnell JR, Xu C, Lutz RA, Chou JJ, Wucherpfennig KW. The structure of the zetazeta transmembrane dimer reveals features essential for its assembly with the T cell receptor. Cell. 2006;127(2):355-68. doi: 10.1016/j.cell.2006.08.044. PubMed PMID: 17055436.
  35. Nadezhdin KD, Bocharova OV, Bocharov EV, Arseniev AS. Dimeric structure of transmembrane domain of amyloid precursor protein in micellar environment. FEBS Lett. 2012;586(12):1687-92. doi: 10.1016/j.febslet.2012.04.062. PubMed PMID: 22584060.
  36. Chen W, Gamache E, Rosenman DJ, Xie J, Lopez MM, Li YM, Wang C. Familial Alzheimer's mutations within APPTM increase Abeta42 production by enhancing accessibility of epsilon-cleavage site. Nat Commun. 2014;5:3037. doi: 10.1038/ncomms4037. PubMed PMID: 24390130.
  37. Decock M, Stanga S, Octave JN, Dewachter I, Smith SO, Constantinescu SN, Kienlen-Campard P. Glycines from the APP GxxxG/GxxxA Transmembrane Motifs Promote Formation of Pathogenic Abeta Oligomers in Cells. Frontiers in aging neuroscience. 2016;8:107. doi: 10.3389/fnagi.2016.00107. PubMed PMID: 27242518.
  38. Decock M, El Haylani L, Stanga S, Dewachter I, Octave JN, Smith SO, Constantinescu SN, Kienlen-Campard P. Analysis by a highly sensitive split luciferase assay of the regions involved in APP dimerization and its impact on processing. FEBS Open Bio. 2015;5:763-73. doi: 10.1016/j.fob.2015.09.002. PubMed PMID: 26500837.
  39. Munter LM, Voigt P, Harmeier A, Kaden D, Gottschalk KE, Weise C, Pipkorn R, Schaefer M, Langosch D, Multhaup G. GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42. EMBO J. 2007;26(6):1702-12. doi: 10.1038/sj.emboj.7601616. PubMed PMID: 17332749.
  40. Gorman PM, Kim S, Guo M, Melnyk RA, McLaurin J, Fraser PE, Bowie JU, Chakrabartty A. Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants. BMC Neuroscience. 2008;9. doi: 10.1186/1471-2202-9-17. PubMed PMID: 18234110.
  41. Wang H, Barreyro L, Provasi D, Djemil I, Torres-Arancivia C, Filizola M, Ubarretxena-Belandia I. Molecular determinants and thermodynamics of the amyloid precursor protein transmembrane domain implicated in Alzheimer's disease. J Mol Biol. 2011;408(5):879-95. doi: 10.1016/j.jmb.2011.03.028. PubMed PMID: 21440556.
  42. Call ME, Wucherpfennig KW, Chou JJ. The structural basis for intramembrane assembly of an activating immunoreceptor complex. Nat Immunol. 2010;11(11):1023-9. doi: 10.1038/ni.1943. PubMed PMID: 20890284.
  43. Wei P, Zheng BK, Guo PR, Kawakami T, Luo SZ. The association of polar residues in the DAP12 homodimer: TOXCAT and molecular dynamics simulation studies. Biophys J. 2013;104(7):1435-44. doi: 10.1016/j.bpj.2013.01.054. PubMed PMID: 23561520.
  44. Fleming KG, Engelman DM. Specificity in transmembrane helix-helix interactions can define a hierarchy of stability for sequence variants. Proc Natl Acad Sci U S A. 2001;98(25):14340-4. doi: 10.1073/pnas.251367498. PubMed PMID: 11724930.
  45. Lemmon MA, Flanagan JM, Treutlein HR, Zhang J, Engelman DM. Sequence specificity in the dimerization of transmembrane alpha-helices. Biochemistry. 1992;31(51):12719-25. PubMed PMID: 1463743.
  46. MacKenzie KR, Prestegard JH, Engelman DM. A transmembrane helix dimer: structure and implications. Science. 1997;276(5309):131-3. PubMed PMID: 9082985.
  47. Mineev KS, Bocharov EV, Volynsky PE, Goncharuk MV, Tkach EN, Ermolyuk YS, Schulga AA, Chupin VV, Maslennikov IV, Efremov RG, Arseniev AS. Dimeric structure of the transmembrane domain of glycophorin a in lipidic and detergent environments. Acta naturae. 2011;3(2):90-8. PubMed PMID: 22649687.
  48. Trenker R, Call ME, Call MJ. Crystal Structure of the Glycophorin A Transmembrane Dimer in Lipidic Cubic Phase. J Am Chem Soc. 2015;137(50):15676-9. doi: 10.1021/jacs.5b11354. PubMed PMID: 26642914.
  49. Finger C, Volkmer T, Prodohl A, Otzen DE, Engelman DM, Schneider D. The stability of transmembrane helix interactions measured in a biological membrane. J Mol Biol. 2006;358(5):1221-8. doi: 10.1016/j.jmb.2006.02.065. PubMed PMID: 16574146.
  50. Duong MT, Jaszewski TM, Fleming KG, MacKenzie KR. Changes in apparent free energy of helix-helix dimerization in a biological membrane due to point mutations. J Mol Biol. 2007;371(2):422-34. doi: 10.1016/j.jmb.2007.05.026. PubMed PMID: 17570394.
  51. Schneider D, Engelman DM. GALLEX, a measurement of heterologous association of transmembrane helices in a biological membrane. J Biol Chem. 2003;278(5):3105-11. doi: 10.1074/jbc.M206287200. PubMed PMID: 12446730.
  52. Bocharov EV, Pustovalova YE, Pavlov KV, Volynsky PE, Goncharuk MV, Ermolyuk YS, Karpunin DV, Schulga AA, Kirpichnikov MP, Efremov RG, Maslennikov IV, Arseniev AS. Unique dimeric structure of BNip3 transmembrane domain suggests membrane permeabilization as a cell death trigger. Journal of Biological Chemistry. 2007;282(22):16256-66. doi: 10.1074/jbc.M701745200. PubMed PMID: 17412696.
  53. Sulistijo ES, MacKenzie KR. Structural basis for dimerization of the BNIP3 transmembrane domain. Biochemistry. 2009;48(23):5106-20. doi: 10.1021/bi802245u. PubMed PMID: 19415897.
  54. Sulistijo ES, MacKenzie KR. Sequence dependence of BNIP3 transmembrane domain dimerization implicates side-chain hydrogen bonding and a tandem GxxxG motif in specific helix-helix interactions. J Mol Biol. 2006;364(5):974-90. doi: 10.1016/j.jmb.2006.09.065. PubMed PMID: 17049556.
  55. Lawrie CM, Sulistijo ES, MacKenzie KR. Intermonomer hydrogen bonds enhance GxxxG-driven dimerization of the BNIP3 transmembrane domain: roles for sequence context in helix-helix association in membranes. J Mol Biol. 2010;396(4):924-36. doi: 10.1016/j.jmb.2009.12.023. PubMed PMID: 20026130.
  56. Sulistijo ES, Jaszewski TM, MacKenzie KR. Sequence-specific dimerization of the transmembrane domain of the "BH3-only" protein BNIP3 in membranes and detergent. J Biol Chem. 2003;278(51):51950-6. doi: 10.1074/jbc.M308429200. PubMed PMID: 14532263.
  57. Chin CN, Sachs JN, Engelman DM. Transmembrane homodimerization of receptor-like protein tyrosine phosphatases. FEBS Lett. 2005;579(17):3855-8. doi: 10.1016/j.febslet.2005.05.071. PubMed PMID: 15978577.
  58. Ruan W, Becker V, Klingmuller U, Langosch D. The interface between self-assembling erythropoietin receptor transmembrane segments corresponds to a membrane-spanning leucine zipper. J Biol Chem. 2004;279(5):3273-9. doi: 10.1074/jbc.M309311200. PubMed PMID: 14602718.
  59. Kubatzky KF, Ruan W, Gurezka R, Cohen J, Ketteler R, Watowich SS, Neumann D, Langosch D, Klingmuller U. Self assembly of the transmembrane domain promotes signal transduction through the erythropoietin receptor. Curr Biol : CB. 2001;11(2):110-5. PubMed PMID: 11231127.
  60. Constantinescu SN, Keren T, Socolovsky M, Nam H, Henis YI, Lodish HF. Ligand-independent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain. Proc Natl Acad Sci U S A. 2001;98(8):4379-84. doi: 10.1073/pnas.081069198. PubMed PMID: 11296286.
  61. Cohen EB, Jun SJ, Bears Z, Barrera FN, Alonso M, Engelman DM, DiMaio D. Mapping the homodimer interface of an optimized, artificial, transmembrane protein activator of the human erythropoietin receptor. PLoS One. 2014;9(4):e95593. doi: 10.1371/journal.pone.0095593. PubMed PMID: 24788775.
  62. Leroy E, Defour JP, Sato T, Dass S, Gryshkova V, Shwe MM, Staerk J, Constantinescu SN, Smith SO. His499 Regulates Dimerization and Prevents Oncogenic Activation by Asparagine Mutations of the Human Thrombopoietin Receptor. J Biol Chem. 2016;291(6):2974-87. doi: 10.1074/jbc.M115.696534. PubMed PMID: 26627830.
  63. Defour JP, Itaya M, Gryshkova V, Brett IC, Pecquet C, Sato T, Smith SO, Constantinescu SN. Tryptophan at the transmembrane-cytosolic junction modulates thrombopoietin receptor dimerization and activation. Proc Natl Acad Sci U S A. 2013;110(7):2540-5. doi: 10.1073/pnas.1211560110. PubMed PMID: 23359689.
  64. Matthews EE, Thevenin D, Rogers JM, Gotow L, Lira PD, Reiter LA, Brissette WH, Engelman DM. Thrombopoietin receptor activation: transmembrane helix dimerization, rotation, and allosteric modulation. FASEB J. 2011;25(7):2234-44. doi: 10.1096/fj.10-178673. PubMed PMID: 21402716.
  65. Parrish HL, Glassman CR, Keenen MM, Deshpande NR, Bronnimann MP, Kuhns MS. A Transmembrane Domain GGxxG Motif in CD4 Contributes to Its Lck-Independent Function but Does Not Mediate CD4 Dimerization. PLoS One. 2015;10(7):e0132333. doi: 10.1371/journal.pone.0132333. PubMed PMID: 26147390.
  66. Lawson EL, Mills DR, Brilliant KE, Hixson DC. The transmembrane domain of CEACAM1-4S is a determinant of anchorage independent growth and tumorigenicity. PLoS One. 2012;7(1):e29606. doi: 10.1371/journal.pone.0029606. PubMed PMID: 22235309.
  67. Patel PC, Lee HS, Ming AY, Rath A, Deber CM, Yip CM, Rocheleau JV, Gray-Owen SD. Inside-out signaling promotes dynamic changes in the carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) oligomeric state to control its cell adhesion properties. J Biol Chem. 2013;288(41):29654-69. doi: 10.1074/jbc.M113.504639. PubMed PMID: 24005674.
  68. Kirrbach J, Krugliak M, Ried CL, Pagel P, Arkin IT, Langosch D. Self-interaction of transmembrane helices representing pre-clusters from the human single-span membrane proteins. Bioinformatics. 2013;29(13):1623-30. doi: 10.1093/bioinformatics/btt247. PubMed PMID: 23640719.
  69. Benej M, Fekecsova S, Poturnajova M. Assessing the effect of RET transmembrane domain mutations in receptor self-association capability using the in vivo TOXCAT system. Neoplasma. 2013;60(1):111-20. doi: 10.4149/neo_2013_015. PubMed PMID: 23067224.
  70. Kjaer S, Kurokawa K, Perrinjaquet M, Abrescia C, Ibanez CF. Self-association of the transmembrane domain of RET underlies oncogenic activation by MEN2A mutations. Oncogene. 2006;25(53):7086-95. doi: 10.1038/sj.onc.1209698. PubMed PMID: 16732321.
  71. Khadria AS, Mueller BK, Stefely JA, Tan CH, Pagliarini DJ, Senes A. A Gly-zipper motif mediates homodimerization of the transmembrane domain of the mitochondrial kinase ADCK3. J Am Chem Soc. 2014;136(40):14068-77. doi: 10.1021/ja505017f. PubMed PMID: 25216398.
  72. Bi G, Liebrand TW, Bye RR, Postma J, van der Burgh AM, Robatzek S, Xu X, Joosten MH. SOBIR1 requires the GxxxG dimerization motif in its transmembrane domain to form constitutive complexes with receptor-like proteins. Mol Plant Pathol. 2016;17(1):96-107. doi: 10.1111/mpp.12266. PubMed PMID: 25891985.
  73. Stokes KD, Rao AG. The role of individual amino acids in the dimerization of CR4 and ACR4 transmembrane domains. Arch Biochem Biophys. 2010;502(2):104-11. doi: 10.1016/ PubMed PMID: 20655866.
  74. Stokes KD, Gururaj Rao A. Dimerization properties of the transmembrane domains of Arabidopsis CRINKLY4 receptor-like kinase and homologs. Arch Biochem Biophys. 2008;477(2):219-26. doi: 10.1016/ PubMed PMID: 18539132.
  75. Noordeen NA, Carafoli F, Hohenester E, Horton MA, Leitinger B. A transmembrane leucine zipper is required for activation of the dimeric receptor tyrosine kinase DDR1. J Biol Chem. 2006;281(32):22744-51. doi: 10.1074/jbc.M603233200. PubMed PMID: 16774916.
  76. Li R, Gorelik R, Nanda V, Law PB, Lear JD, DeGrado WF, Bennett JS. Dimerization of the transmembrane domain of Integrin alphaIIb subunit in cell membranes. J Biol Chem. 2004;279(25):26666-73. doi: 10.1074/jbc.M314168200. PubMed PMID: 15067009.
  77. Luo BH, Springer TA, Takagi J. A specific interface between integrin transmembrane helices and affinity for ligand. PLoS biology. 2004;2(6):e153. doi: 10.1371/journal.pbio.0020153. PubMed PMID: 15208712.
  78. Li W, Metcalf DG, Gorelik R, Li R, Mitra N, Nanda V, Law PB, Lear JD, Degrado WF, Bennett JS. A push-pull mechanism for regulating integrin function. Proc Natl Acad Sci U S A. 2005;102(5):1424-9. doi: 10.1073/pnas.0409334102. PubMed PMID: 15671157.
  79. Yin H, Litvinov RI, Vilaire G, Zhu H, Li W, Caputo GA, Moore DT, Lear JD, Weisel JW, Degrado WF, Bennett JS. Activation of platelet alphaIIbbeta3 by an exogenous peptide corresponding to the transmembrane domain of alphaIIb. J Biol Chem. 2006;281(48):36732-41. doi: 10.1074/jbc.M605877200. PubMed PMID: 17032655.
  80. Li R, Mitra N, Gratkowski H, Vilaire G, Litvinov R, Nagasami C, Weisel JW, Lear JD, DeGrado WF, Bennett JS. Activation of integrin alphaIIbbeta3 by modulation of transmembrane helix associations. Science. 2003;300(5620):795-8. doi: 10.1126/science.1079441. PubMed PMID: 12730600.
  81. Zhu H, Metcalf DG, Streu CN, Billings PC, Degrado WF, Bennett JS. Specificity for homooligomer versus heterooligomer formation in integrin transmembrane helices. J Mol Biol. 2010;401(5):882-91. doi: 10.1016/j.jmb.2010.06.062. PubMed PMID: 20615419.
  82. Roth L, Nasarre C, Dirrig-Grosch S, Aunis D, Cremel G, Hubert P, Bagnard D. Transmembrane domain interactions control biological functions of neuropilin-1. Mol Biol Cell. 2008;19(2):646-54. doi: 10.1091/mbc.E07-06-0625. PubMed PMID: 18045991.
  83. Aci-Seche S, Sawma P, Hubert P, Sturgis JN, Bagnard D, Jacob L, Genest M, Garnier N. Transmembrane recognition of the semaphorin co-receptors neuropilin 1 and plexin A1: coarse-grained simulations. PLoS One. 2014;9(5):e97779. doi: 10.1371/journal.pone.0097779. PubMed PMID: 24858828.
  84. Paulhe F, Wehrle-Haller M, Jacquier MC, Imhof BA, Tabone-Eglinger S, Wehrle-Haller B. Dimerization of Kit-ligand and efficient cell-surface presentation requires a conserved Ser-Gly-Gly-Tyr motif in its transmembrane domain. FASEB J. 2009;23(9):3037-48. doi: 10.1096/fj.09-129577. PubMed PMID: 19386768.
  85. Zhang L, Polyansky A, Buck M. Modeling transmembrane domain dimers/trimers of plexin receptors: implications for mechanisms of signal transmission across the membrane. PLoS One. 2015;10(4):e0121513. doi: 10.1371/journal.pone.0121513. PubMed PMID: 25837709.
  86. Kwon MJ, Park J, Jang S, Eom CY, Oh ES. The Conserved Phenylalanine in the Transmembrane Domain Enhances Heteromeric Interactions of Syndecans. J Biol Chem. 2016;291(2):872-81. doi: 10.1074/jbc.M115.685040. PubMed PMID: 26601939.
  87. Kwon MJ, Choi Y, Yun JH, Lee W, Han IO, Oh ES. A unique phenylalanine in the transmembrane domain strengthens homodimerization of the syndecan-2 transmembrane domain and functionally regulates syndecan-2. J Biol Chem. 2015;290(9):5772-82. doi: 10.1074/jbc.M114.599845. PubMed PMID: 25572401.
  88. Dews IC, Mackenzie KR. Transmembrane domains of the syndecan family of growth factor coreceptors display a hierarchy of homotypic and heterotypic interactions. Proc Natl Acad Sci U S A. 2007;104(52):20782-7. doi: 10.1073/pnas.0708909105. PubMed PMID: 18093920.
  89. Asundi VK, Carey DJ. Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region. J Biol Chem. 1995;270(44):26404-10. PubMed PMID: 7592855.
  90. Wei P, Liu X, Hu MH, Zuo LM, Kai M, Wang R, Luo SZ. The dimerization interface of the glycoprotein Ibbeta transmembrane domain corresponds to polar residues within a leucine zipper motif. Protein Sci. 2011;20(11):1814-23. doi: 10.1002/pro.713. PubMed PMID: 21830242.
  91. Luo SZ, Li R. Specific heteromeric association of four transmembrane peptides derived from platelet glycoprotein Ib-IX complex. J Mol Biol. 2008;382(2):448-57. doi: 10.1016/j.jmb.2008.07.037. PubMed PMID: 18674540.
  92. King G, Dixon AM. Evidence for role of transmembrane helix-helix interactions in the assembly of the Class II major histocompatibility complex. Mol Biosyst. 2010;6(9):1650-61. doi: 10.1039/c002241a. PubMed PMID: 20379596.
  93. Cosson P, Bonifacino JS. Role of transmembrane domain interactions in the assembly of class II MHC molecules. Science. 1992;258(5082):659-62. PubMed PMID: 1329208.
  94. Dawson JP, Melnyk RA, Deber CM, Engelman DM. Sequence context strongly modulates association of polar residues in transmembrane helices. J Mol Biol. 2003;331(1):255-62. PubMed PMID: 12875850.
  95. Plotkowski ML, Kim S, Phillips ML, Partridge AW, Deber CM, Bowie JU. Transmembrane domain of myelin protein zero can form dimers: possible implications for myelin construction. Biochemistry. 2007;46(43):12164-73. doi: 10.1021/bi701066h. PubMed PMID: 17915947.
  96. Xu L, Hu T-T, Luo S-Z. Leucine Zipper Motif Drives the Transmembrane Domain Dimerization of E-cadherin. International Journal of Peptide Research and Therapeutics. 2014;20(1):95-102. doi: 10.1007/s10989-013-9371-y.
  97. Covino R., et al. A eukaryotic sensor for membrane lipid saturation. Mol Cell, 63 (2016) 49-59.
  98. LaPointe LM, Taylor KC, Subramaniam S, Khadria A, Rayment I, Senes A. Structural organization of FtsB, a transmembrane protein of the bacterial divisome. Biochemistry. 2013;52(15):2574-85. doi: 10.1021/bi400222r. PubMed PMID: 23520975.
  99. Armstrong CR, Senes A. Screening for transmembrane association in divisome proteins using TOXGREEN, a high-throughput variant of the TOXCAT assay. Biochim Biophys Acta. 2016;1858(11):2573-83. doi: 10.1016/j.bbamem.2016.07.008. PubMed PMID: 27453198.
  100. Warren G, Oates J, Robinson C, Dixon AM. Contributions of the transmembrane domain and a key acidic motif to assembly and function of the TatA complex. J Mol Biol. 2009;388(1):122-32. doi: 10.1016/j.jmb.2009.02.060. PubMed PMID: 19268473.
  101. Bowen ME, Engelman DM, Brunger AT. Mutational analysis of synaptobrevin transmembrane domain oligomerization. Biochemistry. 2002;41(52):15861-6. PubMed PMID: 12501216.
  102. Laage R, Rohde J, Brosig B, Langosch D. A conserved membrane-spanning amino acid motif drives homomeric and supports heteromeric assembly of presynaptic SNARE proteins. J Biol Chem. 2000;275(23):17481-7. doi: 10.1074/jbc.M910092199. PubMed PMID: 10764817.
  103. Gurezka R, Laage R, Brosig B, Langosch D. A heptad motif of leucine residues found in membrane proteins can drive self-assembly of artificial transmembrane segments. J Biol Chem. 1999;274(14):9265-70. PubMed PMID: 10092601.
  104. Roy R, Laage R, Langosch D. Synaptobrevin transmembrane domain dimerization-revisited. Biochemistry. 2004;43(17):4964-70. doi: 10.1021/bi0362875. PubMed PMID: 15109254.
  105. Kroch AE, Fleming KG. Alternate interfaces may mediate homomeric and heteromeric assembly in the transmembrane domains of SNARE proteins. J Mol Biol. 2006;357(1):184-94. doi: 10.1016/j.jmb.2005.12.060. PubMed PMID: 16427079.
  106. Barwe SP, Kim S, Rajasekaran SA, Bowie JU, Rajasekaran AK. Janus model of the Na,K-ATPase beta-subunit transmembrane domain: distinct faces mediate alpha/beta assembly and beta-beta homo-oligomerization. J Mol Biol. 2007;365(3):706-14. doi: 10.1016/j.jmb.2006.10.029. PubMed PMID: 17078968.
  107. Weber M, Schneider D. Six amino acids define a minimal dimerization sequence and stabilize a transmembrane helix dimer by close packing and hydrogen bonding. FEBS Lett. 2013;587(11):1592-6. doi: 10.1016/j.febslet.2013.03.039. PubMed PMID: 23583446.
  108. Prodohl A, Weber M, Dreher C, Schneider D. A mutational study of transmembrane helix-helix interactions. Biochimie. 2007;89(11):1433-7. doi: 10.1016/j.biochi.2007.06.006. PubMed PMID: 17688996.
  109. Volkmer T, Becker C, Prodohl A, Finger C, Schneider D. Assembly of a transmembrane b-type cytochrome is mainly driven by transmembrane helix interactions. Biochim Biophys Acta. 2006;1758(11):1815-22. doi: 10.1016/j.bbamem.2006.05.009. PubMed PMID: 16860778.
  110. Ried CL, Scharnagl C, Langosch D. Entrapment of Water at the Transmembrane Helix-Helix Interface of Quiescin Sulfhydryl Oxidase 2. Biochemistry. 2016;55(9):1287-90. doi: 10.1021/acs.biochem.5b01239. PubMed PMID: 26894260.
  111. Ried CL, Kube S, Kirrbach J, Langosch D. Homotypic interaction and amino acid distribution of unilaterally conserved transmembrane helices. J Mol Biol. 2012;420(3):251-7. doi: 10.1016/j.jmb.2012.04.008. PubMed PMID: 22561134.
  112. Chung KM, Cheng JH, Suen CS, Huang CH, Tsai CH, Huang LH, Chen YR, Wang AH, Jiaang WT, Hwang MJ, Chen X. The dimeric transmembrane domain of prolyl dipeptidase DPP-IV contributes to its quaternary structure and enzymatic activities. Protein Sci. 2010;19(9):1627-38. doi: 10.1002/pro.443. PubMed PMID: 20572019.
  113. Hower AE, Beltran PJ, Bixby JL. Dimerization of tyrosine phosphatase PTPRO decreases its activity and ability to inactivate TrkC. J Neurochem. 2009;110(5):1635-47. doi: 10.1111/j.1471-4159.2009.06261.x. PubMed PMID: 19573017.
  114. Gadd SL, Clevenger CV. Ligand-independent dimerization of the human prolactin receptor isoforms: functional implications. Mol Endocrinol. 2006;20(11):2734-46. doi: 10.1210/me.2006-0114. PubMed PMID: 16840534.
  115. Chua AO, Chizzonite R, Desai BB, Truitt TP, Nunes P, Minetti LJ, Warrier RR, Presky DH, Levine JF, Gately MK, et al. Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130. J Immunol. 1994;153(1):128-36. PubMed PMID: 7911493.
  116. Schuster B, Meinert W, Rose-John S, Kallen KJ. The human interleukin-6 (IL-6) receptor exists as a preformed dimer in the plasma membrane. FEBS Lett. 2003;538(1-3):113-6. PubMed PMID: 12633863.
  117. Malka Y, Hornakova T, Royer Y, Knoops L, Renauld JC, Constantinescu SN, Henis YI. Ligand-independent homomeric and heteromeric complexes between interleukin-2 or -9 receptor subunits and the gamma chain. J Biol Chem. 2008;283(48):33569-77. doi: 10.1074/jbc.M803125200. PubMed PMID: 18829468.
  118. Singer KL, Mostov KE. Dimerization of the polymeric immunoglobulin receptor controls its transcytotic trafficking. Mol Biol Cell. 1998;9(4):901-15. PubMed PMID: 9529387.
  119. White KE, Cabral JM, Davis SI, Fishburn T, Evans WE, Ichikawa S, Fields J, Yu X, Shaw NJ, McLellan NJ, McKeown C, Fitzpatrick D, Yu K, Ornitz DM, Econs MJ. Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet. 2005;76(2):361-7. doi: 10.1086/427956. PubMed PMID: 15625620.
  120. Przylepa KA, Paznekas W, Zhang M, Golabi M, Bias W, Bamshad MJ, Carey JC, Hall BD, Stevenson R, Orlow S, Cohen MM, Jr., Jabs EW. Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome. Nat Genet. 1996;13(4):492-4. doi: 10.1038/ng0896-492. PubMed PMID: 8696350.
  121. Massague J, Pilch PF, Czech MP. A unique proteolytic cleavage site on the beta subunit of the insulin receptor. J Biol Chem. 1981;256(7):3182-90. PubMed PMID: 7009609.
  122. Anbazhagan V, Munz C, Tome L, Schneider D. Fluidizing the membrane by a local anesthetic: phenylethanol affects membrane protein oligomerization. J Mol Biol. 2010;404(5):773-7. doi: 10.1016/j.jmb.2010.10.026. PubMed PMID: 20970426.
  123. Zhang B, Roth RA. The insulin receptor-related receptor. Tissue expression, ligand binding specificity, and signaling capabilities. J Biol Chem. 1992;267(26):18320-8. PubMed PMID: 1326521.
  124. Cho H, Lamarca R, Chan C. Oligomerization of the transmembrane domain of IRE1alpha in SDS micelles. Biochem Biophys Res Commun. 2012;427(4):764-7. doi: 10.1016/j.bbrc.2012.09.135. PubMed PMID: 23041190.
  125. Petrova IM, Lahaye LL, Martianez T, de Jong AW, Malessy MJ, Verhaagen J, Noordermeer JN, Fradkin LG. Homodimerization of the Wnt receptor DERAILED recruits the Src family kinase SRC64B. Mol Cell Biol. 2013;33(20):4116-27. doi: 10.1128/mcb.00169-13. PubMed PMID: 23979591.
  126. Ogawa H, Qiu Y, Ogata CM, Misono KS. Crystal structure of hormone-bound atrial natriuretic peptide receptor extracellular domain: rotation mechanism for transmembrane signal transduction. J Biol Chem. 2004;279(27):28625-31. doi: 10.1074/jbc.M313222200. PubMed PMID: 15117952.
  127. Shen J, Maruyama IN. Nerve growth factor receptor TrkA exists as a preformed, yet inactive, dimer in living cells. FEBS Lett. 2011;585(2):295-9. doi: 10.1016/j.febslet.2010.12.031. PubMed PMID: 21187090.
  128. Shen J, Maruyama IN. Brain-derived neurotrophic factor receptor TrkB exists as a preformed dimer in living cells. J Mol Signal. 2012;7(1):2. doi: 10.1186/1750-2187-7-2. PubMed PMID: 22269274.
  129. Latz E, Verma A, Visintin A, Gong M, Sirois CM, Klein DC, Monks BG, McKnight CJ, Lamphier MS, Duprex WP, Espevik T, Golenbock DT. Ligand-induced conformational changes allosterically activate Toll-like receptor 9. Nat Immunol. 2007;8(7):772-9. doi: 10.1038/ni1479. PubMed PMID: 17572678.
  130. Parthasarathy K, Lin X, Tan SM, Law SK, Torres J. Transmembrane helices that form two opposite homodimeric interactions: an asparagine scan study of alphaM and beta2 integrins. Protein Sci. 2008;17(5):930-8. doi: 10.1110/ps.073234208. PubMed PMID: 18369198.
  131. Go MY, Kim S, Partridge AW, Melnyk RA, Rath A, Deber CM, Mogridge J. Self-association of the transmembrane domain of an anthrax toxin receptor. J Mol Biol. 2006;360(1):145-56. doi: 10.1016/j.jmb.2006.04.072. PubMed PMID: 16756998.
  132. Marita M, Wang Y, Kaliszewski MJ, Skinner KC, Comar WD, Shi X, Dasari P, Zhang X, Smith AW. Class A Plexins Are Organized as Preformed Inactive Dimers on the Cell Surface. Biophys J. 2015;109(9):1937-45. doi: 10.1016/j.bpj.2015.04.043. PubMed PMID: 26536270.
  133. Ashman JB, Miller J. A role for the transmembrane domain in the trimerization of the MHC class II-associated invariant chain. J Immunol. 1999;163(5):2704-12. PubMed PMID: 10453012.
  134. Dixon AM, Stanley BJ, Matthews EE, Dawson JP, Engelman DM. Invariant chain transmembrane domain trimerization: a step in MHC class II assembly. Biochemistry. 2006;45(16):5228-34. doi: 10.1021/bi052112e. PubMed PMID: 16618111.
  135. Cole G, Simonetti K, Ademi I, Sharpe S. Dimerization of the transmembrane domain of human tetherin in membrane mimetic environments. Biochemistry. 2012;51(25):5033-40. doi: 10.1021/bi201747t. PubMed PMID: 22667354.
  136. Srinivasan S, Deng W, Li R. L-selectin transmembrane and cytoplasmic domains are monomeric in membranes. Biochim Biophys Acta. 2011;1808(6):1709-15. doi: 10.1016/j.bbamem.2011.02.006. PubMed PMID: 21316337.
  137. Toutain CM, Clarke DJ, Leeds JA, Kuhn J, Beckwith J, Holland IB, Jacq A. The transmembrane domain of the DnaJ-like protein DjlA is a dimerisation domain. Mol Genet Genomics : MGG. 2003;268(6):761-70. doi: 10.1007/s00438-002-0793-z. PubMed PMID: 12655402.
  138. Martinez-Garay CA, Juanes MA, Igual JC, Mingarro I, Bano MC. A transmembrane serine residue in the Rot1 protein is essential for yeast cell viability. Biochem J. 2014;458(2):239-49. doi: 10.1042/bj20131306. PubMed PMID: 24303792.
  139. Watt B, Tenza D, Lemmon MA, Kerje S, Raposo G, Andersson L, Marks MS. Mutations in or near the transmembrane domain alter PMEL amyloid formation from functional to pathogenic. PLoS genetics. 2011;7(9):e1002286. doi: 10.1371/journal.pgen.1002286. PubMed PMID: 21949659.
  140. Therien AG, Deber CM. Oligomerization of a peptide derived from the transmembrane region of the sodium pump gamma subunit: effect of the pathological mutation G41R. J Mol Biol. 2002;322(3):583-50. PubMed PMID: 12225751.
  141. Arkin IT, Adams PD, MacKenzie KR, Lemmon MA, Brunger AT, Engelman DM. Structural organization of the pentameric transmembrane alpha-helices of phospholamban, a cardiac ion channel. EMBO J. 1994;13(20):4757-64. PubMed PMID: 7525269.
  142. Oxenoid K, Chou JJ. The structure of phospholamban pentamer reveals a channel-like architecture in membranes. Proc Natl Acad Sci U S A. 2005;102(31):10870-5. doi: 10.1073/pnas.0504920102. PubMed PMID: 16043693.
  143. Simmerman HK, Kobayashi YM, Autry JM, Jones LR. A leucine zipper stabilizes the pentameric membrane domain of phospholamban and forms a coiled-coil pore structure. J Biol Chem. 1996;271(10):5941-6. PubMed PMID: 8621468.
  144. Francis VG, Mohammed AM, Aradhyam GK, Gummadi SN. The single C-terminal helix of human phospholipid scramblase 1 is required for membrane insertion and scrambling activity. FEBS J. 2013;280(12):2855-69. doi: 10.1111/febs.12289. PubMed PMID: 23590222.
  145. Bustos DM, Velours J. The modification of the conserved GxxxG motif of the membrane-spanning segment of subunit g destabilizes the supramolecular species of yeast ATP synthase. J Biol Chem. 2005;280(32):29004-10. doi: 10.1074/jbc.M502140200. PubMed PMID: 15970598.
  146. Lindner E, White SH. Topology, dimerization, and stability of the single-span membrane protein CadC. J Mol Biol. 2014;426(16):2942-57. doi: 10.1016/j.jmb.2014.06.006. PubMed PMID: 24946151.
  147. Glukhov E, Shulga YV, Epand RF, Dicu AO, Topham MK, Deber CM, Epand RM. Membrane interactions of the hydrophobic segment of diacylglycerol kinase epsilon. Biochim Biophys Acta. 2007;1768(10):2549-58. doi: 10.1016/j.bbamem.2007.06.012. PubMed PMID: 17669357.
  148. Garg P, Nemec KN, Khaled AR, Tatulian SA. Transmembrane pore formation by the carboxyl terminus of Bax protein. Biochim Biophys Acta. 2013;1828(2):732-42. doi: 10.1016/j.bbamem.2012.08.006. PubMed PMID: 22906710.
  149. Peter B, Ngubane NC, Fanucchi S, Dirr HW. Membrane mimetics induce helix formation and oligomerization of the chloride intracellular channel protein 1 transmembrane domain. Biochemistry. 2013;52(16):2739-49. doi: 10.1021/bi4002776. PubMed PMID: 23547926.
  150. Peter B, Polyansky AA, Fanucchi S, Dirr HW. A Lys-Trp cation-pi interaction mediates the dimerization and function of the chloride intracellular channel protein 1 transmembrane domain. Biochemistry. 2014;53(1):57-67. doi: 10.1021/bi401433f. PubMed PMID: 24328417.