Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province/Key Laboratory of Growth Regulation and Transformation Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang, China; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang Province, China.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Trends Biochem Sci. 2021 Jun;46(6):489-501. doi: 10.1016/j.tibs.2020.11.009. Epub 2020 Dec 22.
Historically, ryanodine receptors (RyRs) have presented unique challenges for high-resolution structural determination despite long-standing interest in their role in excitation-contraction coupling. Owing to their large size (nearly 2.2 MDa), high-resolution structures remained elusive until the advent of cryogenic electron microscopy (cryo-EM) techniques. In recent years, structures for both RyR1 and RyR2 have been solved at near-atomic resolution. Furthermore, recent reports have delved into their more complex structural associations with key modulators - proteins such as the dihydropyridine receptor (DHPR), FKBP12/12.6, and calmodulin (CaM), as well as ions and small molecules including Ca, ATP, caffeine, and PCB95. This review addresses the modulation of RyR1 and RyR2, in addition to the impact of such discoveries on intracellular Ca dynamics and biophysical properties.
从历史上看，尽管人们对肌浆网 Ca2+ 释放通道（ryanodine receptors，RyRs）在兴奋-收缩耦联中的作用很感兴趣，但由于其分子量较大（近 2.2 MDa），因此其高分辨率结构一直难以确定。直到低温电子显微镜（cryogenic electron microscopy，cryo-EM）技术的出现，才得以解决。近年来，RyR1 和 RyR2 的结构已接近原子分辨率。此外，最近的报道还深入研究了它们与关键调节剂（如二氢吡啶受体（dihydropyridine receptor，DHPR）、FKBP12/12.6 和钙调蛋白（calmodulin，CaM））以及离子和小分子（如 Ca2+、ATP、咖啡因和 PCB95）的更复杂的结构关联。本文除了探讨 RyR1 和 RyR2 的调节作用外，还探讨了这些发现对细胞内 Ca2+ 动力学和生物物理特性的影响。
