EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular basis for gating of cardiac ryanodine receptor explains the mechanisms for gain- and loss-of function mutations.
ジャーナル・号・ページ	Nat Commun, Vol. 13, Issue 1, Page 2821, Year 2022
掲載日	2022年5月20日
著者	Takuya Kobayashi / Akihisa Tsutsumi / Nagomi Kurebayashi / Kei Saito / Masami Kodama / Takashi Sakurai / Masahide Kikkawa / Takashi Murayama / Haruo Ogawa /
PubMed 要旨	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 ...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.
リンク	Nat Commun / PubMed:35595836 / PubMed Central
手法	EM (単粒子)
解像度	3.3 - 3.72 Å
構造データ	32036 7vmr EMDB-32036, PDB-7vmr: Structure of recombinant RyR2 mutant K4593A (EGTA dataset) 手法: EM (単粒子) / 解像度: 3.3 Å 33935 7vml EMDB-33935, PDB-7vml: Structure of recombinant RyR2 (EGTA dataset, class 1&2, closed state) 手法: EM (単粒子) / 解像度: 3.3 Å 33936 7vmm EMDB-33936, PDB-7vmm: Structure of recombinant RyR2 (EGTA dataset, class 1, closed state) 手法: EM (単粒子) / 解像度: 3.49 Å 33937 7vmn EMDB-33937, PDB-7vmn: Structure of recombinant RyR2 (EGTA dataset, class 2, closed state) 手法: EM (単粒子) / 解像度: 3.52 Å 33938 7vmo EMDB-33938, PDB-7vmo: Structure of recombinant RyR2 (Ca2+ dataset, class 1, open state) 手法: EM (単粒子) / 解像度: 3.45 Å 33939 7vmp EMDB-33939, PDB-7vmp: Structure of recombinant RyR2 (Ca2+ dataset, class 2, open state) 手法: EM (単粒子) / 解像度: 3.51 Å EMDB-33940: Structure of recombinant RyR2 (Ca2+ dataset, class 3, open state) 手法: EM (単粒子) / 解像度: 3.72 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-CA: Unknown entry / カルシウムジカチオン
由来	mus musculus (ハツカネズミ) homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / CALCIUM (カルシウム) / CALCIUM CHANNEL (カルシウムチャネル) / CALCIUM TRANSPORT / ION TRANSPORT / IONIC CHANNEL (イオンチャネル) / METAL TRANSPORT / ER/SR MEMBRANE / RYANODINE RECEPTOR (リアノジン受容体) / RYANODINE (リアノジン) / RECEPTOR (受容体) / WILD TYPE (野生型)