7VML

Structure of recombinant RyR2 (EGTA dataset, class 1&2, closed state)

これはPDB形式変換不可エントリーです。

7VML の概要

• エントリーDOI: 10.2210/pdb7vml/pdb
• EMDBエントリー: 33935
• 分子名称: Ryanodine receptor 2, Peptidyl-prolyl cis-trans isomerase FKBP1B, ZINC ION (3 entities in total)
• 機能のキーワード: calcium, calcium channel, calcium transport, ion transport, ionic channel, metal transport, er/sr membrane, ryanodine receptor, ryanodine, receptor, wild type, membrane protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 2210813.15

構造登録者

Kobayashi, T.,Tsutsumi, A.,Kurebayashi, N.,Kodama, M.,Kikkawa, M.,Murayama, T.,Ogawa, H. (登録日: 2021-10-09, 公開日: 2022-08-10, 最終更新日: 2024-06-19)

主引用文献

Kobayashi, T.,Tsutsumi, A.,Kurebayashi, N.,Saito, K.,Kodama, M.,Sakurai, T.,Kikkawa, M.,Murayama, T.,Ogawa, H.
Molecular basis for gating of cardiac ryanodine receptor explains the mechanisms for gain- and loss-of function mutations.
Nat Commun, 13:2821-2821, 2022

PubMed Abstract: Cardiac ryanodine receptor (RyR2) is a large Ca release channel in the sarcoplasmic reticulum and indispensable for excitation-contraction coupling in the heart. RyR2 is activated by Ca and RyR2 mutations are implicated in severe arrhythmogenic diseases. Yet, the structural basis underlying channel opening and how mutations affect the channel remains unknown. Here, we address the gating mechanism of RyR2 by combining high-resolution structures determined by cryo-electron microscopy with quantitative functional analysis of channels carrying various mutations in specific residues. We demonstrated two fundamental mechanisms for channel gating: interactions close to the channel pore stabilize the channel to prevent hyperactivity and a series of interactions in the surrounding regions is necessary for channel opening upon Ca binding. Mutations at the residues involved in the former and the latter mechanisms cause gain-of-function and loss-of-function, respectively. Our results reveal gating mechanisms of the RyR2 channel and alterations by pathogenic mutations at the atomic level.

PubMed: 35595836
DOI: 10.1038/s41467-022-30429-x

実験手法

ELECTRON MICROSCOPY (3.3 Å)