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	Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.
ジャーナル・号・ページ	Sci Adv, Vol. 8, Issue 29, Page eabo1272, Year 2022
掲載日	2022年7月22日
著者	Marco C Miotto / Gunnar Weninger / Haikel Dridi / Qi Yuan / Yang Liu / Anetta Wronska / Zephan Melville / Leah Sittenfeld / Steven Reiken / Andrew R Marks /
PubMed 要旨	Ryanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT ...Ryanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT results from stress-induced sarcoplasmic reticular Ca leak via the mutant RyR2 channels during diastole. We present atomic models of human wild-type (WT) RyR2 and the CPVT mutant RyR2-R2474S determined by cryo-electron microscopy with overall resolutions in the range of 2.6 to 3.6 Å, and reaching local resolutions of 2.25 Å, unprecedented for RyR2 channels. Under nonactivating conditions, the RyR2-R2474S channel is in a "primed" state between the closed and open states of WT RyR2, rendering it more sensitive to activation that results in stress-induced Ca leak. The Rycal drug ARM210 binds to RyR2-R2474S, reverting the primed state toward the closed state. Together, these studies provide a mechanism for CPVT and for the therapeutic actions of ARM210.
リンク	Sci Adv / PubMed:35857850 / PubMed Central
手法	EM (単粒子)
解像度	2.58 - 3.69 Å
構造データ	EMDB-26139: Structure of human RyR2 in the closed state. 手法: EM (単粒子) / 解像度: 3.53 Å 26405 7u9q EMDB-26405, PDB-7u9q: Structure of PKA phosphorylated human RyR2 in the closed state 手法: EM (単粒子) / 解像度: 3.11 Å 26407 7u9r EMDB-26407, PDB-7u9r: Structure of PKA phosphorylated human RyR2 in the open state 手法: EM (単粒子) / 解像度: 3.69 Å 26408 7u9t EMDB-26408, PDB-7u9t: Structure of PKA phosphorylated human RyR2 in the closed state in the presence of Calmodulin 手法: EM (単粒子) / 解像度: 2.68 Å 26409 7u9x EMDB-26409, PDB-7u9x: Structure of PKA phosphorylated human RyR2-R2474S in the closed state 手法: EM (単粒子) / 解像度: 2.58 Å 26410 7u9z EMDB-26410, PDB-7u9z: Structure of PKA phosphorylated human RyR2-R2474S in the open state 手法: EM (単粒子) / 解像度: 3.29 Å 26412 7ua1 EMDB-26412, PDB-7ua1: Structure of PKA phosphorylated human RyR2-R2474S in the closed state in the presence of ARM210 手法: EM (単粒子) / 解像度: 2.99 Å 26413 7ua3 EMDB-26413, PDB-7ua3: Structure of PKA phosphorylated human RyR2-R2474S in the closed state in the presence of Calmodulin 手法: EM (単粒子) / 解像度: 2.97 Å 26414 7ua4 EMDB-26414, PDB-7ua4: Structure of PKA phosphorylated human RyR2-R2474S in the open state in the presence of Calmodulin 手法: EM (単粒子) / 解像度: 2.93 Å 26415 7ua5 EMDB-26415, PDB-7ua5: Structure of dephosphorylated human RyR2 in the closed state 手法: EM (単粒子) / 解像度: 2.83 Å 26416 7ua9 EMDB-26416, PDB-7ua9: Structure of dephosphorylated human RyR2 in the open state 手法: EM (単粒子) / 解像度: 3.59 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-XAN: XANTHINE / キサンチン ChemComp-KVR: 4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)methyl]benzoic acid ChemComp-HOH*: WATER
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / calcium channel / Ryanodine receptor 2