Title |
Structure of a mammalian ryanodine receptor
|
---|---|
Published in |
Nature, December 2014
|
DOI | 10.1038/nature13950 |
Pubmed ID | |
Authors |
Ran Zalk, Oliver B. Clarke, Amédée des Georges, Robert A. Grassucci, Steven Reiken, Filippo Mancia, Wayne A. Hendrickson, Joachim Frank, Andrew R. Marks |
Abstract |
Ryanodine receptors (RyRs) mediate the rapid release of calcium (Ca(2+)) from intracellular stores into the cytosol, which is essential for numerous cellular functions including excitation-contraction coupling in muscle. Lack of sufficient structural detail has impeded understanding of RyR gating and regulation. Here we report the closed-state structure of the 2.3-megadalton complex of the rabbit skeletal muscle type 1 RyR (RyR1), solved by single-particle electron cryomicroscopy at an overall resolution of 4.8 Å. We fitted a polyalanine-level model to all 3,757 ordered residues in each protomer, defining the transmembrane pore in unprecedented detail and placing all cytosolic domains as tertiary folds. The cytosolic assembly is built on an extended α-solenoid scaffold connecting key regulatory domains to the pore. The RyR1 pore architecture places it in the six-transmembrane ion channel superfamily. A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF-hands originating from the α-solenoid scaffold, suggesting a mechanism for channel gating by Ca(2+). |
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Demographic breakdown
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Scientists | 1 | 9% |
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France | 2 | <1% |
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Researcher | 68 | 18% |
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Student > Bachelor | 38 | 10% |
Professor | 17 | 4% |
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Unknown | 55 | 14% |
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Physics and Astronomy | 11 | 3% |
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Unknown | 68 | 18% |