Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská Cesta 21, 845 51 Bratislava, Slovakia.
Molecules. 2020 Sep 4;25(18):4040. doi: 10.3390/molecules25184040.
Cardiac arrhythmias are serious, life-threatening diseases associated with the dysregulation of Ca2+ influx into the cytoplasm of cardiomyocytes. This dysregulation often arises from dysfunction of ryanodine receptor 2 (RyR2), the principal Ca2+ release channel. Dysfunction of RyR1, the skeletal muscle isoform, also results in less severe, but also potentially life-threatening syndromes. The and genes have been found to harbor three main mutation "hot spots", where mutations change the channel structure, its interdomain interface properties, its interactions with its binding partners, or its dynamics. In all cases, the result is a defective release of Ca2+ ions from the sarcoplasmic reticulum into the myocyte cytoplasm. Here, we provide an overview of the most frequent diseases resulting from mutations to RyR1 and RyR2, briefly review some of the recent experimental structural work on these two molecules, detail some of the computational work describing their dynamics, and summarize the known changes to the structure and function of these receptors with particular emphasis on their N-terminal, central, and channel domains.
心律失常是与心肌细胞细胞质内钙离子内流失调相关的严重的、危及生命的疾病。这种失调通常是由于兰尼碱受体 2（RyR2），即主要的钙离子释放通道的功能障碍引起的。骨骼肌同工型 RyR1 的功能障碍也会导致不那么严重但也可能危及生命的综合征。已经发现 和 基因有三个主要的突变“热点”，突变会改变通道结构、其域间界面特性、与结合伴侣的相互作用或其动力学。在所有情况下，结果都是肌浆网中钙离子从肌浆网向肌细胞细胞质的释放缺陷。在这里，我们概述了由 RyR1 和 RyR2 突变引起的最常见疾病，简要回顾了这两个分子的一些最新实验结构研究，详细介绍了一些描述其动力学的计算工作，并总结了这些受体的结构和功能的已知变化，特别强调了它们的 N 端、中央和通道结构域。
