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Structure of rabbit ryanodine receptor RyR1 open state activated by calcium ion
Structural highlights
FunctionRYR1_RABIT Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).[1] [2] Publication Abstract from PubMedRyanodine receptors (RyRs) are a class of giant ion channels with molecular mass over 2.2 mega-Daltons. These channels mediate calcium signaling in a variety of cells. Since more than 80% of the RyR protein is folded into the cytoplasmic assembly and the remaining residues form the transmembrane domain, it has been hypothesized that the activation and regulation of RyR channels occur through an as yet uncharacterized long-range allosteric mechanism. Here we report the characterization of a Ca(2+)-activated open-state RyR1 structure by cryo-electron microscopy. The structure has an overall resolution of 4.9 A and a resolution of 4.2 A for the core region. In comparison with the previously determined apo/closed-state structure, we observed long-range allosteric gating of the channel upon Ca(2+) activation. In-depth structural analyses elucidated a novel channel-gating mechanism and a novel ion selectivity mechanism of RyR1. Our work not only provides structural insights into the molecular mechanisms of channel gating and regulation of RyRs, but also sheds light on structural basis for channel-gating and ion selectivity mechanisms for the six-transmembrane-helix cation channel family. Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1.,Wei R, Wang X, Zhang Y, Mukherjee S, Zhang L, Chen Q, Huang X, Jing S, Liu C, Li S, Wang G, Xu Y, Zhu S, Williams AJ, Sun F, Yin CC Cell Res. 2016 Sep;26(9):977-94. doi: 10.1038/cr.2016.99. Epub 2016 Aug 30. PMID:27573175[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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