The Central domain of RyR1 is the transducer for long-range allosteric gating of channel opening

Xiao Chen Bai, Zhen Yan, Jianping Wu, Zhangqiang Li, Nieng Yan

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

The ryanodine receptors (RyRs) are intracellular calcium channels responsible for rapid release of Ca 2+ from the sarcoplasmic/endoplasmic reticulum (SR/ER) to the cytoplasm, which is essential for the excitation-contraction (E-C) coupling of cardiac and skeletal muscles. The near-atomic resolution structure of closed RyR1 revealed the molecular details of this colossal channel, while the long-range allosteric gating mechanism awaits elucidation. Here, we report the cryo-EM structures of rabbit RyR1 in three closed conformations at about 4 Å resolution and an open state at 5.7 Å. Comparison of the closed RyR1 structures shows a breathing motion of the cytoplasmic platform, while the channel domain and its contiguous Central domain remain nearly unchanged. Comparison of the open and closed structures shows a dilation of the S6 tetrahelical bundle at the cytoplasmic gate that leads to channel opening. During the pore opening, the cytoplasmic "O-ring" motif of the channel domain and the U-motif of the Central domain exhibit coupled motion, while the Central domain undergoes domain-wise displacement. These structural analyses provide important insight into the E-C coupling in skeletal muscles and identify the Central domain as the transducer that couples the conformational changes of the cytoplasmic platform to the gating of the central pore.

Original languageEnglish (US)
Pages (from-to)995-1006
Number of pages12
JournalCell Research
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • RyR1
  • calcium channel
  • excitation-contraction coupling
  • membrane transport
  • voltage-gated calcium channels

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