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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.
Recent advances in cryogenic electron microscopy (cryo-EM) have enabled high-resolution structural determination of ryanodine receptors (RyRs). These structures reveal complex associations with modulators, impacting intracellular calcium dynamics.
Area of Science:
- Biophysics
- Molecular Biology
- Structural Biology
Background:
- Ryanodine receptors (RyRs) are critical for excitation-contraction coupling but historically challenging to study structurally.
- Their large size (~2.2 MDa) hindered high-resolution analysis until recent technological advancements.
Purpose of the Study:
- To review recent structural insights into RyR1 and RyR2.
- To explore the impact of these structures on understanding RyR modulation and function.
Main Methods:
- Cryogenic electron microscopy (cryo-EM) techniques.
- Analysis of structural data for RyR1 and RyR2.
Main Results:
- Near-atomic resolution structures of RyR1 and RyR2 have been determined.
- These structures elucidate interactions with key modulators like DHPR, FKBP12/12.6, CaM, Ca2+, ATP, caffeine, and PCB95.
Conclusions:
- Structural determination of RyRs has significantly advanced understanding of their function.
- These findings impact knowledge of intracellular calcium dynamics and biophysical properties.
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