7wi4
Cryo-EM structure of E.Coli FtsH protease cytosolic domainsCryo-EM structure of E.Coli FtsH protease cytosolic domains
Structural highlights
Function[FTSH_ECOLI] 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.[1] [2] [3] [4] 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).[5] [6] [7] [8] Publication Abstract from PubMedThe membrane-bound AAA protease FtsH is the key player controlling protein quality in bacteria. Two single-pass membrane proteins, HflK and HflC, interact with FtsH to modulate its proteolytic activity. Here, we present structure of the entire FtsH-HflKC complex, comprising 12 copies of both HflK and HflC, all of which interact reciprocally to form a cage, as well as four FtsH hexamers with periplasmic domains and transmembrane helices enclosed inside the cage and cytoplasmic domains situated at the base of the cage. FtsH K61/D62/S63 in the beta2-beta3 loop in the periplasmic domain directly interact with HflK, contributing to complex formation. Pull-down and in vivo enzymatic activity assays validate the importance of the interacting interface for FtsH-HflKC complex formation. Structural comparison with the substrate-bound human m-AAA protease AFG3L2 offers implications for the HflKC cage in modulating substrate access to FtsH. Together, our findings provide a better understanding of FtsH-type AAA protease holoenzyme assembly and regulation. Cryo-EM structure of the entire FtsH-HflKC AAA protease complex.,Qiao Z, Yokoyama T, Yan XF, Beh IT, Shi J, Basak S, Akiyama Y, Gao YG Cell Rep. 2022 May 31;39(9):110890. doi: 10.1016/j.celrep.2022.110890. PMID:35649372[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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