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| Title | Cryo-EM Structure of the FtsH Periplasmic Domain Reveals Functional Dynamics. |
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| Journal, issue, pages | ACS Chem Biol, Vol. 21, Issue 4, Page 844-851, Year 2026 |
| Publish date | Apr 17, 2026 |
Authors | Günce Göc / Sathish K N Yadav / George Orriss / Ufuk Borucu / Imre Berger / Christiane Schaffitzel / Burak V Kabasakal / ![]() |
| PubMed Abstract | 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 ...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 links | ACS Chem Biol / PubMed:41944809 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.9 - 9.3 Å |
| Structure data | ![]() EMDB-66013: Cryo-EM Map of the Periplasmic Domain of AAA Protease FtsH in a Novel Orientation ![]() EMDB-66014: Cryo-EM Map of the Transmembrane Domain of AAA Protease FtsH in a Novel Orientation ![]() EMDB-66015: Cryo-EM Map of Transmembrane Domain of AAA+ protease FtsH EMDB-66269, PDB-9wus: |
| Source |
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Keywords | MEMBRANE PROTEIN / AAA+ Protease / Transmembrane Domain FtsH |
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