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

作　　者：Xiao-Chen Bai Zhen Yan Jianping Wu Zhangqiang Li Nieng Yan 

机构地区：[1]MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK [2]State Key Laboratory of Membrane Biology,School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [3]Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [4]Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China

出　　处：《Cell Research》2016年第9期995-1006,共12页细胞研究（英文版）

基　　金：Acknowledgments We thank the Tsinghua University Branch of China National Center for Protein Sciences （Beijing） for providing the facility support. This work was supported by the Ministry of Science and Technology of China （2015CB9101012014 and ZX09507003006）, and the National Natural Science Foundation of China （31321062 and 81590761）. The research of Nieng Yan was supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institute and an endowed professorship from Bayer Healthcare.

摘　　要：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 RyRI 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 A° resolution and an open state at 5.7 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.

关 键 词：RyRI calcium channel excitation-contraction coupling membrane transport voltage-gated calcium channels 

分 类 号：Q[生物学]