Cryo-EM structure of transmembrane AAA+ protease FtsH in the ADP state

Liu, Wu; Schoonen, Martien; Wang, Tong; McSweeney, Sean; Liu, Qun

doi:10.1038/s42003-022-03213-2

Title: Cryo-EM structure of transmembrane AAA+ protease FtsH in the ADP state

Journal Article · Wed Mar 23 00:00:00 EDT 2022 · Communications Biology

DOI:https://doi.org/10.1038/s42003-022-03213-2· OSTI ID:1856266

Liu, Wu; Schoonen, Martien;

; McSweeney, Sean;

Abstract AAA+ proteases regulate numerous physiological and cellular processes through tightly regulated proteolytic cleavage of protein substrates driven by ATP hydrolysis. FtsH is the only known family of membrane-anchored AAA+ proteases essential for membrane protein quality control. Although a spiral staircase rotation mechanism for substrate translocation across the FtsH pore has been proposed, the detailed conformational changes among various states have not been clear due to absence of FtsH structures in these states. We report here the cryo-EM structure for Thermotoga maritima FtsH ( Tm FtsH) in a fully ADP-bound symmetric state. Comparisons of the ADP-state structure with its apo-state and a substrate-engaged yeast YME1 structure show conformational changes in the ATPase domains, rather than the protease domains. A reconstruction of the full-length Tm FtsH provides structural insights for the dynamic transmembrane and the periplasmic domains. Our structural analyses expand the understanding of conformational switches between different nucleotide states in ATP hydrolysis by FtsH.

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Research Organization:: Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC0012704

OSTI ID:: 1856266

Alternate ID(s):: OSTI ID: 1855083

Report Number(s):: BNL-222816-2022-JAAM; 257; PII: 3213

Journal Information:: Communications Biology, Journal Name: Communications Biology Vol. 5 Journal Issue: 1; ISSN 2399-3642

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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Title: Cryo-EM structure of transmembrane AAA+ protease FtsH in the ADP state

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