7wi4

Cryo-EM structure of E.Coli FtsH protease cytosolic domains

spinqualitylabelsall models 7wi4, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7wi4 is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ANP, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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). Publication Abstract from PubMed The 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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