7W71

Crystal structure of the PDZ-C domain of E. coli RseP in complex with 12C7 Fab

7W71 の概要

• エントリーDOI: 10.2210/pdb7w71/pdb
• 分子名称: Regulator of sigma-E protease RseP, Heavy chain of Fab, Light chain of Fab (3 entities in total)
• 機能のキーワード: intramembrane protease, hydrolase, hydrolase-immune system complex, hydrolase/immune system
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 113722.73

構造登録者

Hirose, T.,Katagiri, S.,Nogi, T. (登録日: 2021-12-02, 公開日: 2022-09-07, 最終更新日: 2024-10-30)

主引用文献

Imaizumi, Y.,Takanuki, K.,Miyake, T.,Takemoto, M.,Hirata, K.,Hirose, M.,Oi, R.,Kobayashi, T.,Miyoshi, K.,Aruga, R.,Yokoyama, T.,Katagiri, S.,Matsuura, H.,Iwasaki, K.,Kato, T.,Kaneko, M.K.,Kato, Y.,Tajiri, M.,Akashi, S.,Nureki, O.,Hizukuri, Y.,Akiyama, Y.,Nogi, T.
Mechanistic insights into intramembrane proteolysis by E. coli site-2 protease homolog RseP.
Sci Adv, 8:eabp9011-eabp9011, 2022

PubMed 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 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.

PubMed: 36001659
DOI: 10.1126/sciadv.abp9011

実験手法

X-RAY DIFFRACTION (3.2 Å)