An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins
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Author(s)
Ghanbarpour, Alireza
Telusma, Bertina
Powell, Barrett M.
Zhang, Jia J.
Bolstad, Isabella
Vargas, Carolyn
Keller, Sandro
Baker, Tania A.
Sauer, Robert T.
Davis, Joseph H.
Date Issued
March 13, 2025
Journal
The EMBO Journal
Publisher
Nature Publishing Group UK
Citation
Ghanbarpour, Alireza, Telusma, Bertina, Powell, Barrett M., Zhang, Jia J., Bolstad, Isabella et al. 2025. "An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins." The EMBO Journal, 44.
Version
Final published version
Abstract
The AAA protease FtsH associates with HflK/C subunits to form a megadalton-size complex that spans the inner membrane and extends into the periplasm of E. coli. How this bacterial complex and homologous assemblies in eukaryotic organelles recruit, extract, and degrade membrane-embedded substrates is unclear. Following the overproduction of protein components, recent cryo-EM structures showed symmetric HflK/C cages surrounding FtsH in a manner proposed to inhibit the degradation of membrane-embedded substrates. Here, we present structures of native protein complexes, in which HflK/C instead forms an asymmetric nautilus-shaped assembly with an entryway for membrane-embedded substrates to reach and be engaged by FtsH. Consistent with this nautilus-like structure, proteomic assays suggest that HflK/C enhances FtsH degradation of certain membrane-embedded substrates. Membrane curvature in our FtsH•HflK/C complexes is opposite that of surrounding membrane regions, a property that correlates with lipid scramblase activity and possibly with FtsH’s function in the degradation of membrane-embedded proteins.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Computational and Systems Biology Program
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DOI of Published Version
https://doi.org/10.1038/s44318-025-00408-1
