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Updated: Nov 24, 2025

Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Structural Basis for the Modulation of Ryanodine Receptors
Deshun Gong1, Nieng Yan2, Hannah A Ledford2
1Zhejiang 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.
Abstract:
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 Ca2+, ATP, caffeine, and PCB95. This review addresses the modulation of RyR1 and RyR2, in addition to the impact of such discoveries on intracellular Ca2+ dynamics and biophysical properties.
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