FTSH_ECOLI » ATP-dependent zinc metalloprotease FtsH

FTSH_ECOLI » ATP-dependent zinc metalloprotease FtsH
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Topology in Bacterial Gram-negative inner membrane
Topologyextracellular side
cytoplasmic side
FTSH_ECOLI » ATP-dependent zinc metalloprotease FtsH » Cell division protease FtsH
Hydrophobic Thickness 30.4 ± 3.2 Å
Tilt Angle 25 ± 4°
ΔGtransfer -22.7 kcal/mol
ΔGfold -18.8 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING
Topology Out
TM Segments 98-120 (94-124)
Pathways none
PDB 4v0b (A/B/C=25-96), 1lv7 (A=141-395)
OPM 1lv7, 3kds (THEMA)
Complexes none
Interactions

HFLC, Complex: HFLC:FTSH, PubMed

HFLK, Complex: HFLK:FTSH, PubMed

PBPA, Complex: FTSH:PBPA, PubMed

Domains

AA: 5-93, PDBID: 4V0B, Subunit C, Seq Identity:100%, FtsH Extracellular

AA: 188-321, PDBID: 1LV7, Subunit A, Seq Identity:100%, ATPase family associated with various cellular activities (AAA)

AA: 381-592, PDBID: 1LV7, Subunit A, Seq Identity:100%, Peptidase family M41

UniProt annotation for FTSH_ECOLI » ATP-dependent zinc metalloprotease FtsH
FUNCTION: Acts as a processive, ATP-dependent zinc metallopeptidase for both cytoplasmic and membrane proteins. Plays a role in the quality control of integral membrane proteins. Degrades a few membrane proteins that have not been assembled into complexes such as SecY, F(0) ATPase subunit a and YccA, and also cytoplasmic proteins sigma-32, LpxC, KdtA and phage lambda cII protein among others. Degrades membrane proteins in a processive manner starting at either the N- or C-terminus; recognition requires a cytoplasmic tail of about 20 residues with no apparent sequence requirements. It presumably dislocates membrane-spanning and periplasmic segments of the protein into the cytoplasm to degrade them, this probably requires ATP. Degrades C-terminal- tagged cytoplasmic proteins which are tagged with an 11-amino-acid nonpolar destabilizing tail via a mechanism involving the 10SA (SsrA) stable RNA.

FUNCTION: As FtsH regulates the levels of both LpxC and KdtA it is required for synthesis of both the protein and lipid components of lipopolysaccharide (LPS).

ENZYME REGULATION: Activity against phage lambda cII protein is inhibited by EDTA but not by PMSF. In vitro pre-incubation of FtsH with HflKC abolishes its activity against phage lambda cII protein; Cytoplasmic side.

SUBUNIT: The E.coli AAA domain has been modeled as a homohexamer, in Thermus thermophilus the same domain crystallizes as a homohexamer. Forms a complex with HflKC (formerly called HflA); complex formation is stimulated by ATP. Interacts with YccA, and probably weakly with QmcA. Can be cross-linked to YidC (OxaA) and to a nascent polypeptide chain for an integral membrane protein.

MISCELLANEOUS: The ftsH gene was discovered independently through 3 different phenotypes and received 3 different names: ftsH, for filamentous temperature-sensitive; tolZ, for colicin tolerance, and hlfB, because mutants show a high frequency of lysogenization when infected with phage lambda.

MISCELLANEOUS: Requires ATP for protease catalytic activity, probably due to tight coupling of the 2 activities; ADP or non- hydrolyzable analogs cannot substitute, except when unfolded, non- physiological substrates are tested.

UniProt features for FTSH_ECOLI » ATP-dependent zinc metalloprotease FtsH
CHAIN 1 644 ATP-dependent zinc metalloprotease FtsH.
ACT_SITE 415 415
SITE 225 225 Substrate binding.
Amino Acid Sequence for FTSH_ECOLI » ATP-dependent zinc metalloprotease FtsH
MAKNLILWLV IAVVLMSVFQ SFGPSESNGR KVDYSTFLQE VNNDQVREAR INGREINVTK KDSNRYTTYI PVQDPKLLDN LLTKNVKVVG EPPEEPSLLA SIFISWFPML LLIGVWIFFM RQMQGGGGKG AMSFGKSKAR MLTEDQIKTT FADVAGCDEA KEEVAELVEY LREPSRFQKL GGKIPKGVLM VGPPGTGKTL LAKAIAGEAK VPFFTISGSD FVEMFVGVGA SRVRDMFEQA KKAAPCIIFI DEIDAVGRQR GAGLGGGHDE REQTLNQMLV EMDGFEGNEG IIVIAATNRP DVLDPALLRP GRFDRQVVVG LPDVRGREQI LKVHMRRVPL APDIDAAIIA RGTPGFSGAD LANLVNEAAL FAARGNKRVV SMVEFEKAKD KIMMGAERRS MVMTEAQKES TAYHEAGHAI IGRLVPEHDP VHKVTIIPRG RALGVTFFLP EGDAISASRQ KLESQISTLY GGRLAEEIIY GPEHVSTGAS NDIKVATNLA RNMVTQWGFS EKLGPLLYAE EEGEVFLGRS VAKAKHMSDE TARIIDQEVK ALIERNYNRA RQLLTDNMDI LHAMKDALMK YETIDAPQID DLMARRDVRP PAGWEEPGAS NNSGDNGSPK APRPVDEPRT PNPGNTMSEQ LGDK