Cryo-EM structure of the entire FtsH-HflKC AAA protease complex.
Cell Rep
; 39(9): 110890, 2022 05 31.
Article
in En
| MEDLINE
| ID: mdl-35649372
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 ß2-ß3 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Escherichia coli Proteins
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2022
Document type:
Article
Affiliation country:
Singapur