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

Zhen Yan, Xiao Chen Bai, Chuangye Yan, Jianping Wu, Zhangqiang Li, Tian Xie, Wei Peng, Chang Cheng Yin, Xueming Li, Sjors H.W. Scheres, Yigong Shi, Nieng Yan

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

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 organizationandapproximately 5,000residues ineachprotomer.Herewe report the structure of the rabbitRyR1 incomplex with its modulator FKBP12 at an overall resolution of 3.8A° , determined by single-particle electron cryomicroscopy. 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.Anegative-charge-enrichedhairpin loop connecting S5 andthe porehelix 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 themembrane. Allosteric regulation of the pore by the cytoplasmic domains ismediated 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.

Original languageEnglish (US)
Pages (from-to)50-55
Number of pages6
JournalNature
Volume517
Issue number7532
DOIs
StatePublished - Jan 1 2015

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Ryanodine Receptor Calcium Release Channel
Allosteric Regulation
Rabbits
Ion Channels
Tacrolimus Binding Protein 1A
Armadillos
Cryoelectron Microscopy
S 6
Excitation Contraction Coupling
Myocardium
Skeletal Muscle
Ions

ASJC Scopus subject areas

  • General

Cite this

Yan, Z., Bai, X. C., Yan, C., Wu, J., Li, Z., Xie, T., ... Yan, N. (2015). Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. Nature, 517(7532), 50-55. https://doi.org/10.1038/nature14063

Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. / Yan, Zhen; Bai, Xiao Chen; Yan, Chuangye; Wu, Jianping; Li, Zhangqiang; Xie, Tian; Peng, Wei; Yin, Chang Cheng; Li, Xueming; Scheres, Sjors H.W.; Shi, Yigong; Yan, Nieng.

In: Nature, Vol. 517, No. 7532, 01.01.2015, p. 50-55.

Research output: Contribution to journalArticle

Yan, Z, Bai, XC, Yan, C, Wu, J, Li, Z, Xie, T, Peng, W, Yin, CC, Li, X, Scheres, SHW, Shi, Y & Yan, N 2015, 'Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution', Nature, vol. 517, no. 7532, pp. 50-55. https://doi.org/10.1038/nature14063
Yan, Zhen ; Bai, Xiao Chen ; Yan, Chuangye ; Wu, Jianping ; Li, Zhangqiang ; Xie, Tian ; Peng, Wei ; Yin, Chang Cheng ; Li, Xueming ; Scheres, Sjors H.W. ; Shi, Yigong ; Yan, Nieng. / Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. In: Nature. 2015 ; Vol. 517, No. 7532. pp. 50-55.
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