Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution

The ryanodine receptors (RyRs) are high-conductance intracellular Ca2+ channels that play a pivotal role in the excitation-contraction coupling of skeletal and cardiac muscles. RyRs are the largest known ion channels, with a homotetrameric organization and approximately 5000 residues in each protome...

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Main Authors:	Yan, Zhen, Bai, Xiaochen, Yan, Chuangye, Wu, Jianping, Li, Zhangqiang, Xie, Tian, Peng, Wei, Yin, Changcheng, Li, Xueming, Scheres, Sjors H.W., Shi, Yigong, Yan, Nieng
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338550/

id	pubmed-4338550
recordtype	oai_dc
spelling	pubmed-43385502015-07-01 Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution Yan, Zhen Bai, Xiaochen Yan, Chuangye Wu, Jianping Li, Zhangqiang Xie, Tian Peng, Wei Yin, Changcheng Li, Xueming Scheres, Sjors H.W. Shi, Yigong Yan, Nieng Article The ryanodine receptors (RyRs) are high-conductance intracellular Ca2+ channels that play a pivotal role in the excitation-contraction coupling of skeletal and cardiac muscles. RyRs are the largest known ion channels, with a homotetrameric organization and approximately 5000 residues in each protomer. Here we report the structure of the rabbit RyR1 in complex with its modulator FKBP12 at an overall resolution of 3.8 Å, determined by single-particle electron cryo-microscopy. Three previously uncharacterized domains, named Central, Handle, and Helical domains, display the armadillo repeat fold. These domains, together with the amino-terminal domain, constitute a network of superhelical scaffold for binding and propagation of conformational changes. The channel domain exhibits the voltage-gated ion channel superfamily fold with distinct features. A negative charge-enriched hairpin loop connecting S5 and the pore helix is positioned above the entrance to the selectivity filter vestibule. The four elongated S6 segments form a right-handed helical bundle that closes the pore at the cytoplasmic border of the membrane. Allosteric regulation of the pore by the cytoplasmic domains is mediated through extensive interactions between the Central domains and the channel domain. These structural features explain high ion conductance by RyRs and the long-range allosteric regulation of channel activities. 2014-12-15 2015-01-01 /pmc/articles/PMC4338550/ /pubmed/25517095 http://dx.doi.org/10.1038/nature14063 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yan, Zhen Bai, Xiaochen Yan, Chuangye Wu, Jianping Li, Zhangqiang Xie, Tian Peng, Wei Yin, Changcheng Li, Xueming Scheres, Sjors H.W. Shi, Yigong Yan, Nieng
spellingShingle	Yan, Zhen Bai, Xiaochen Yan, Chuangye Wu, Jianping Li, Zhangqiang Xie, Tian Peng, Wei Yin, Changcheng Li, Xueming Scheres, Sjors H.W. Shi, Yigong Yan, Nieng Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution
author_facet	Yan, Zhen Bai, Xiaochen Yan, Chuangye Wu, Jianping Li, Zhangqiang Xie, Tian Peng, Wei Yin, Changcheng Li, Xueming Scheres, Sjors H.W. Shi, Yigong Yan, Nieng
author_sort	Yan, Zhen
title	Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution
title_short	Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution
title_full	Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution
title_fullStr	Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution
title_full_unstemmed	Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution
title_sort	structure of the rabbit ryanodine receptor ryr1 at near-atomic resolution
description	The ryanodine receptors (RyRs) are high-conductance intracellular Ca2+ channels that play a pivotal role in the excitation-contraction coupling of skeletal and cardiac muscles. RyRs are the largest known ion channels, with a homotetrameric organization and approximately 5000 residues in each protomer. Here we report the structure of the rabbit RyR1 in complex with its modulator FKBP12 at an overall resolution of 3.8 Å, determined by single-particle electron cryo-microscopy. Three previously uncharacterized domains, named Central, Handle, and Helical domains, display the armadillo repeat fold. These domains, together with the amino-terminal domain, constitute a network of superhelical scaffold for binding and propagation of conformational changes. The channel domain exhibits the voltage-gated ion channel superfamily fold with distinct features. A negative charge-enriched hairpin loop connecting S5 and the pore helix is positioned above the entrance to the selectivity filter vestibule. The four elongated S6 segments form a right-handed helical bundle that closes the pore at the cytoplasmic border of the membrane. Allosteric regulation of the pore by the cytoplasmic domains is mediated through extensive interactions between the Central domains and the channel domain. These structural features explain high ion conductance by RyRs and the long-range allosteric regulation of channel activities.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338550/
_version_	1613191896088182784

Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution

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