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

Commun Biol. 2022 Mar 23;5(1):257. doi: 10.1038/s42003-022-03213-2.


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 (TmFtsH) 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 TmFtsH 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATP-Dependent Proteases* / metabolism
  • ATPases Associated with Diverse Cellular Activities / chemistry
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Adenosine Diphosphate
  • Adenosine Triphosphate / metabolism
  • Cryoelectron Microscopy
  • Models, Molecular
  • Protein Conformation
  • Thermotoga maritima*


  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • ATP-Dependent Proteases
  • ATPases Associated with Diverse Cellular Activities