7WI4

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

Summary for 7WI4

• Entry DOI: 10.2210/pdb7wi4/pdb
• EMDB information: 32521
• Descriptor: ATP-dependent zinc metalloprotease FtsH, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ZINC ION, ... (4 entities in total)
• Functional Keywords: complex, membrane protein, hydrolase
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 6
• Total formula weight: 428345.79

Authors

Qiao, Z.,Gao, Y.G. (deposition date: 2022-01-02, release date: 2022-06-01, Last modification date: 2024-06-26)

Primary citation

Qiao, Z.,Yokoyama, T.,Yan, X.F.,Beh, I.T.,Shi, J.,Basak, S.,Akiyama, Y.,Gao, Y.G.
Cryo-EM structure of the entire FtsH-HflKC AAA protease complex.
Cell Rep, 39:110890-110890, 2022

PubMed Abstract: 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 β2-β3 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.

PubMed: 35649372
DOI: 10.1016/j.celrep.2022.110890

Experimental method

ELECTRON MICROSCOPY (3.4 Å)