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

Yuki Imaizumi, Kazunori Takanuki, Takuya Miyake, Mizuki Takemoto, Kunio Hirata, Mika Hirose, Rika Oi, Tatsuya Kobayashi, Kenichi Miyoshi, Rie Aruga, Tatsuhiko Yokoyama, Shizuka Katagiri (+11 others)
2022 bioRxiv   pre-print

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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 E. coli RseP. Our observations are consistent with a rearrangement of the RseP domains surrounding the active center to expose the substrate-binding site where a conserved electrostatic linkage between the transmembrane and
more » ... associated domains mediates the conformational changes, suggesting that RseP has a gating mechanism to regulate substrate entry. Mutational analysis also supports that the substrate transmembrane helix is unwound by strand addition to the intramembrane β sheet and is clamped at the active center for efficient cleavage. Furthermore, this substrate accommodation mechanism appears to be common across distinct intramembrane proteases.
doi:10.1101/2022.01.31.478169 fatcat:6pfcrzu6vncz5je4vg3agjr4ay
Citation

Yuki Imaizumi, Kazunori Takanuki, Takuya Miyake, Mizuki Takemoto, Kunio Hirata, Mika Hirose, Rika Oi, Tatsuya Kobayashi, Kenichi Miyoshi, Rie Aruga, Tatsuhiko Yokoyama, Shizuka Katagiri, Hiroaki Matsuura, Kenji Iwasaki, Takayuki Kato, Mika K. Kaneko, Yukinari Kato, Michiko Tajiri, Satoko Akashi, Osamu Nureki, Yohei Hizukuri, Yoshinori Akiyama, Terukazu Nogi. "Mechanistic insights into intramembrane proteolysis by E. coli site-2 protease homolog RseP." bioRxiv (2022)