7CF9

Structure of RyR1 (Ca2+/CHL)

これはPDB形式変換不可エントリーです。

7CF9 の概要

• エントリーDOI: 10.2210/pdb7cf9/pdb
• EMDBエントリー: 30343
• 分子名称: Ryanodine receptor 1,RyR1, Peptidyl-prolyl cis-trans isomerase FKBP1B, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: rabbit, ryanodine receptor1, chl., membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 2208371.50

構造登録者

Ma, R.,Haji-Ghassemi, O.,Ma, D.,Lin, L.,Samurkas, A.,Van Petegem, F.,Yuchi, Z. (登録日: 2020-06-24, 公開日: 2020-09-02, 最終更新日: 2024-03-27)

主引用文献

Ma, R.,Haji-Ghassemi, O.,Ma, D.,Jiang, H.,Lin, L.,Yao, L.,Samurkas, A.,Li, Y.,Wang, Y.,Cao, P.,Wu, S.,Zhang, Y.,Murayama, T.,Moussian, B.,Van Petegem, F.,Yuchi, Z.
Structural basis for diamide modulation of ryanodine receptor.
Nat.Chem.Biol., 16:1246-1254, 2020

PubMed Abstract: The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the highest-resolution cryo-electron microscopy (cryo-EM) structure of RyR1 in the open state, in complex with the anthranilic diamide chlorantraniliprole (CHL). The 3.2-Å local resolution map facilitates unambiguous assignment of the CHL binding site. The molecule induces a conformational change by affecting the S4-S5 linker, triggering channel opening. The binding site is further corroborated by mutagenesis data, which reveal how diamide insecticides are selective to the Lepidoptera group of insects over honeybee or mammalian RyRs. Our data reveal that several pests have developed resistance via two mechanisms, steric hindrance and loss of contact. Our results provide a foundation for the development of highly selective pesticides aimed at overcoming resistance and therapeutic molecules to treat human myopathies.

PubMed: 32807966
DOI: 10.1038/s41589-020-0627-5

実験手法

ELECTRON MICROSCOPY (4.7 Å)