Cryo-EM Structure of the FtsH Periplasmic Domain Reveals Functional Dynamics
ACS CHEMICAL BIOLOGY, cilt.21, sa.4, ss.844-851, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 21 Sayı: 4
- Basım Tarihi: 2026
- Doi Numarası: 10.1021/acschembio.5c01025
- Dergi Adı: ACS CHEMICAL BIOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
- Sayfa Sayıları: ss.844-851
- Orta Doğu Teknik Üniversitesi Adresli: Evet
Özet
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.