Mechanistic insights into intramembrane proteolysis by E. coli site-2 protease homolog RseP.

ABSTRACT: Site-2 proteases are a conserved family of intramembrane proteases that cleave transmembrane substrates to regulate signal transduction and maintain proteostasis. Here, we elucidated crystal structures of inhibitor-bound forms of bacterial site-2 proteases including Escherichia coli RseP. Structure-based chemical modification and cross-linking experiments indicated that the RseP domains surrounding the active center undergo conformational changes to expose the substrate-binding site, suggesting that RseP has a gating mechanism to regulate substrate entry. Furthermore, mutational analysis suggests that a conserved electrostatic linkage between the transmembrane and peripheral membrane-associated domains mediates the conformational changes. In vivo cleavage assays also support that th

SUBMITTER: Imaizumi Y 

PROVIDER: S-EPMC9401612 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature