9WUS

Cryo-EM Structure of the Periplasmic Domain of AAA Protease FtsH

Summary for 9WUS

• Entry DOI: 10.2210/pdb9wus/pdb
• EMDB information: 66269
• Descriptor: ATP-dependent zinc metalloprotease FtsH (1 entity in total)
• Functional Keywords: aaa+ protease, transmembrane domain ftsh, membrane protein
• Biological source: Escherichia coli
• Total number of polymer chains: 6
• Total formula weight: 45068.10

Authors

Kabasakal, B.V.,Goc, G.,Yadav, S.,Borucu, U.,Berger, I.,Schaffitzel, C. (deposition date: 2025-09-18, release date: 2026-05-13)

Primary citation

Goc, G.,Yadav, S.K.N.,Orriss, G.,Borucu, U.,Berger, I.,Schaffitzel, C.,Kabasakal, B.V.
Cryo-EM Structure of the FtsH Periplasmic Domain Reveals Functional Dynamics.
Acs Chem.Biol., 21:844-851, 2026

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 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.

PubMed: 41944809
DOI: 10.1021/acschembio.5c01025

Experimental method

ELECTRON MICROSCOPY (4.9 Å)