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Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1

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 dom...

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Autores principales: 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 J, Sun, Fei, Yin, Chang-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034117/
https://www.ncbi.nlm.nih.gov/pubmed/27573175
http://dx.doi.org/10.1038/cr.2016.99
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author 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 J
Sun, Fei
Yin, Chang-Cheng
author_facet 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 J
Sun, Fei
Yin, Chang-Cheng
author_sort Wei, Risheng
collection PubMed
description 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 Ca(2+)-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 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.
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spelling pubmed-50341172016-10-04 Structural insights into Ca(2+)-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 J Sun, Fei Yin, Chang-Cheng Cell Res Original Article 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 Ca(2+)-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 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. Nature Publishing Group 2016-09 2016-08-30 /pmc/articles/PMC5034117/ /pubmed/27573175 http://dx.doi.org/10.1038/cr.2016.99 Text en Copyright © 2016 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Article
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 J
Sun, Fei
Yin, Chang-Cheng
Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1
title Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1
title_full Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1
title_fullStr Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1
title_full_unstemmed Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1
title_short Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1
title_sort structural insights into ca(2+)-activated long-range allosteric channel gating of ryr1
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034117/
https://www.ncbi.nlm.nih.gov/pubmed/27573175
http://dx.doi.org/10.1038/cr.2016.99
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