8ZAY

Crystal structure of Fab from mouse monoclonal antibody 4A9 against Aquifex aeolicus RseP PDZ tandem

8ZAY の概要

• エントリーDOI: 10.2210/pdb8zay/pdb
• 分子名称: VH-CH1 region of antibody of anti-RseP orthologue from A aeolicus, Light chain of antibody of anti-RseP orthologue from A aeolicus, ZINC ION, ... (4 entities in total)
• 機能のキーワード: antibody, protein binding
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 96854.91

構造登録者

Adachi, Y.,Nogi, T. (登録日: 2024-04-25, 公開日: 2025-03-05, 最終更新日: 2025-03-12)

主引用文献

Asahi, K.,Hirose, M.,Aruga, R.,Shimizu, Y.,Tajiri, M.,Tanaka, T.,Adachi, Y.,Tanaka, Y.,Kaneko, M.K.,Kato, Y.,Akashi, S.,Akiyama, Y.,Hizukuri, Y.,Kato, T.,Nogi, T.
Cryo-EM structure of the bacterial intramembrane metalloprotease RseP in the substrate-bound state.
Sci Adv, 11:eadu0925-eadu0925, 2025

PubMed 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 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 RseP (RseP) 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 lateral diffusion. Furthermore, in vivo photocrosslinking supported that this substrate accommodation mode is recapitulated on the cell membrane. Our results suggest that the substrate accommodation by threading through a conserved membrane-associated region stabilizes the substrate-complex and contributes to substrate discrimination on the membrane.

PubMed: 40009668
DOI: 10.1126/sciadv.adu0925

実験手法

X-RAY DIFFRACTION (2.3 Å)