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Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein Oligomerization: The Ryanodine Receptor Case Study
Published on: July 27, 2016
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Structural Basis for Gating and Activation of RyR1
Amédée des Georges1, Oliver B Clarke2, Ran Zalk3
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
Cell
|September 24, 2016
Summary
The type-1 ryanodine receptor (RyR1) structure reveals how calcium and ATP binding controls muscle contraction. Cryo-EM shows RyR1 gating involves global and local conformational changes, explaining channel activation.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Physiology
Background:
- The type-1 ryanodine receptor (RyR1) is a critical intracellular calcium release channel.
- RyR1 is essential for skeletal muscle contraction, regulating calcium dynamics.
Purpose of the Study:
- To elucidate the structural mechanisms underlying RyR1 channel gating and activation.
- To identify binding sites for key activators like calcium (Ca2+), ATP, and caffeine.
Main Methods:
- Cryo-electron microscopy (cryo-EM) reconstructions of RyR1 in multiple functional states.
- High-resolution structural analysis of open and closed RyR1 states.
Main Results:
- Identified binding sites for Ca2+, ATP, and caffeine at C-terminal domain interfaces.
- Observed Ca2+ or ATP alone induces "priming" conformational changes without pore dilation.
- Revealed that RyR1 gating involves global cytosolic changes and local transmembrane domain alterations, including S6 bending and pore dilation.
Conclusions:
- The study provides a detailed structural understanding of RyR1 gating and activation.
- Conformational changes in RyR1, driven by ligand binding, are crucial for skeletal muscle function.
Keywords:
RyRcalcium releasecryo-EMexcitation contraction couplinggatingryanodinesingle-particle reconstructionstructureMore Related Videos
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