6WJC

Muscarinic acetylcholine receptor 1 - muscarinic toxin 7 complex

6WJC の概要

• エントリーDOI: 10.2210/pdb6wjc/pdb
• 分子名称: Muscarinic acetylcholine receptor M1,Endolysin fusion, Muscarinic toxin 7, ACETAMIDE, ... (6 entities in total)
• 機能のキーワード: gpcr, natural toxin, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66990.36

構造登録者

Maeda, S.,Kobilka, B.K. (登録日: 2020-04-13, 公開日: 2020-07-08, 最終更新日: 2024-11-13)

主引用文献

Maeda, S.,Xu, J.,N Kadji, F.M.,Clark, M.J.,Zhao, J.,Tsutsumi, N.,Aoki, J.,Sunahara, R.K.,Inoue, A.,Garcia, K.C.,Kobilka, B.K.
Structure and selectivity engineering of the M1muscarinic receptor toxin complex.
Science, 369:161-167, 2020

PubMed Abstract: Muscarinic toxins (MTs) are natural toxins produced by mamba snakes that primarily bind to muscarinic acetylcholine receptors (MAChRs) and modulate their function. Despite their similar primary and tertiary structures, MTs show distinct binding selectivity toward different MAChRs. The molecular details of how MTs distinguish MAChRs are not well understood. Here, we present the crystal structure of MAChR in complex with MT7, a subtype-selective anti-MAChR snake venom toxin. The structure reveals the molecular basis of the extreme subtype specificity of MT7 for MAChR and the mechanism by which it regulates receptor function. Through in vitro engineering of MT7 finger regions that was guided by the structure, we have converted the selectivity from MAChR toward MAChR, suggesting that the three-finger fold is a promising scaffold for developing G protein-coupled receptor modulators.

PubMed: 32646996
DOI: 10.1126/science.aax2517

実験手法

X-RAY DIFFRACTION (2.55 Å)