Cryo-EM structure of the bacterial intramembrane metalloprotease RseP in the substrate-bound state.

ABSTRACT: Site-2 proteases (S2Ps), conserved intramembrane metalloproteases that maintain cellular homeostasis, are associated with chronic infection and persistence leading to multidrug resistance in bacterial pathogens. A structural model of how S2Ps discriminate and accommodate substrates could help us develop selective antimicrobial agents. We previously proposed that the Escherichia coli S2P RseP unwinds helical substrate segments before cleavage, but the mechanism for accommodating a full-length membrane-spanning substrate remained unclear. Our present cryo-EM analysis of Aquifex aeolicus RseP (AaRseP) revealed that a substrate-like membrane protein fragment from the expression host occupied the active site while spanning a transmembrane cavity that is inaccessible via lat

SUBMITTER: Asahi K 

PROVIDER: S-EPMC11864173 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature