@article{168301,
  keywords = {Animals, Models, Molecular, Structure-Activity Relationship, Cytoplasm, Cryoelectron Microscopy, Rabbits, Ion Channel Gating, Protein Domains, Allosteric Regulation, Excitation Contraction Coupling, Ryanodine Receptor Calcium Release Channel},
  author = {Xiao-Chen Bai and Zhen Yan and Jianping Wu and Zhangqiang Li and Nieng Yan},
  title = {The Central domain of RyR1 is the transducer for long-range allosteric gating of channel opening},
  abstract = {<p>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 {\r A} resolution and an open state at 5.7 {\r A}. 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.</p>
},
  year = {2016},
  journal = {Cell Res},
  volume = {26},
  pages = {995-1006},
  month = {09/2016},
  issn = {1748-7838},
  doi = {10.1038/cr.2016.89},
  language = {eng},
}