Cryo-EM Structure of the FtsH Periplasmic Domain Reveals Functional Dynamics
ACS CHEMICAL BIOLOGY, vol.21, no.4, pp.844-851, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 21 Issue: 4
- Publication Date: 2026
- Doi Number: 10.1021/acschembio.5c01025
- Journal Name: ACS CHEMICAL BIOLOGY
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
- Page Numbers: pp.844-851
- Middle East Technical University Affiliated: Yes
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 structures of the Escherichia coli FtsH periplasmic domain (FtsH-PD) revealing insights into its intrinsic conformational flexibility. Our analysis resolved two distinct states: a 4.9 & Aring; structure exhibiting the conserved alpha + beta fold and a 7.3 & Aring; map representing distinct rotated-helix conformation characterized by 20 degrees 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.