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-Structure paper
タイトル | Mechanistic insights into intramembrane proteolysis by site-2 protease homolog RseP. |
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ジャーナル・号・ページ | Sci Adv, Vol. 8, Issue 34, Page eabp9011, Year 2022 |
掲載日 | 2022年8月26日 |
著者 | 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 / |
PubMed 要旨 | 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 ...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 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 the substrate transmembrane helix is unwound by strand addition to the intramembrane β sheet of RseP and is clamped by a conserved asparagine residue at the active center for efficient cleavage. This mechanism underlying the substrate binding, i.e., unwinding and clamping, appears common across distinct families of intramembrane proteases that cleave transmembrane segments. |
リンク | Sci Adv / PubMed:36001659 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.15 - 19.2 Å |
構造データ | EMDB-33409: Detergent-solubilized E. coli RseP in complex with Fab EMDB-33410: Deterget-solubilized E. coli RseP(L358C) mutant in complex with Fab PDB-7w6x: PDB-7w6y: PDB-7w6z: PDB-7w70: PDB-7w71: |
化合物 | ChemComp-ZN: ChemComp-BAT: ChemComp-HOH: |
由来 |
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キーワード | HYDROLASE / Intramembrane protease / HYDROLASE/IMMUNE SYSTEM / HYDROLASE-IMMUNE SYSTEM complex |