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TitleCryo-EM Structure of the FtsH Periplasmic Domain Reveals Functional Dynamics.
Journal, issue, pagesACS Chem Biol, Vol. 21, Issue 4, Page 844-851, Year 2026
Publish dateApr 17, 2026
AuthorsGünce Göc / Sathish K N Yadav / George Orriss / Ufuk Borucu / Imre Berger / Christiane Schaffitzel / Burak V Kabasakal /
PubMed AbstractFtsH, an AAA + metalloprotease that is essential in bacteria and eukaryotic organelles, maintains cellular homeostasis by degrading misfolded and membrane-associated proteins. Here, we report cryo-EM ...FtsH, an AAA + metalloprotease that is essential in bacteria and eukaryotic organelles, maintains cellular homeostasis by degrading misfolded and membrane-associated proteins. Here, we report cryo-EM structures of the FtsH periplasmic domain (FtsH-PD) revealing insights into its intrinsic conformational flexibility. Our analysis resolved two distinct states: a 4.9 Å structure exhibiting the conserved α + β fold and a 7.3 Å map representing distinct rotated-helix conformation characterized by 20° clockwise rotation of two alpha helices. These findings support a model where conformational changes are present not only in the FtsH cytosolic domain but also in the periplasmic domain. This flexibility potentially facilitates substrate translocation through a combination of mechanisms involving both the FtsH-PD and the HflKC complexed with FtsH, along with lipid-scramblase activity, to assist in membrane protein extraction. This study offers new perspectives on how conformational changes in the periplasmic domain contribute to FtsH substrate degradation mechanisms.
External linksACS Chem Biol / PubMed:41944809 / PubMed Central
MethodsEM (single particle)
Resolution4.9 - 9.3 Å
Structure data

EMDB-66013: Cryo-EM Map of the Periplasmic Domain of AAA Protease FtsH in a Novel Orientation
Method: EM (single particle) / Resolution: 7.3 Å

EMDB-66014: Cryo-EM Map of the Transmembrane Domain of AAA Protease FtsH in a Novel Orientation
Method: EM (single particle) / Resolution: 8.2 Å

EMDB-66015: Cryo-EM Map of Transmembrane Domain of AAA+ protease FtsH
Method: EM (single particle) / Resolution: 9.3 Å

EMDB-66269, PDB-9wus:
Cryo-EM Structure of the Periplasmic Domain of AAA Protease FtsH
Method: EM (single particle) / Resolution: 4.9 Å

Source
  • escherichia coli (E. coli)
KeywordsMEMBRANE PROTEIN / AAA+ Protease / Transmembrane Domain FtsH

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