Structural insights into Ca2+-activated long-range allosteric channel gating of RyR1

Wei, Risheng, Wang, Xue, Zhang, Yan, Mukherjee, Saptarshi, Zhang, Lei, Chen, Qiang, Huang, Xinrui, Jing, Shan, Liu, Congcong, Li, Shuang, Wang, Guangyu, Xu, Yaofang, Zhu, Sujie, Williams, Alan John, Sun, Fei and Yin, Chang-Cheng 2016. Structural insights into Ca2+-activated long-range allosteric channel gating of RyR1. Cell Research 26 (9) , pp. 977-994. 10.1038/cr.2016.99

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Abstract

Ryanodine 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 Ca2+-activated open-state RyR1 structure by cryo-electron microscopy. The structure has an overall resolution of 4.9 Å and a resolution of 4.2 Å for the core region. In comparison with the previously determined apo/closed-state structure, we observed long-range allosteric gating of the channel upon Ca2+ 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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 Unported License.
Publisher:	Nature Publishing Group
ISSN:	1001-0602
Date of First Compliant Deposit:	9 July 2019
Date of Acceptance:	3 August 2016
Last Modified:	05 May 2023 00:21
URI:	https://orca.cardiff.ac.uk/id/eprint/94372

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