| Title | Structural insights into Ca2+-activated long-range allosteric channel gating of RyR1 |
| Authors | Wei, Risheng Wang, Xue Zhang, Yan Mukherjee, Saptarshi Zhang, Lei Chen, Qiang Huang, Xinrui Jing, Shan Liu, Congcong Li, Shuang Wang, Guangyu Xu, Yaofang Zhu, Sujie Williams, Alan J. Sun, Fei Yin, Chang-Cheng |
| Affiliation | Peking Univ, Dept Biophys, Hlth Sci Ctr, Beijing 100191, Peoples R China. Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China. Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China. Cardiff Univ, Wales Heart Res Inst, Sch Med, Cardiff CF14 4XN, S Glam, Wales. Peking Univ, Hlth Sci Ctr, Electron Microscopy Anal Lab, Beijing 100191, Peoples R China. Chinese Acad Sci, Inst Biophys, Ctr Biol Imaging, Beijing 100101, Peoples R China. Peking Univ, Ctr Prot Sci, Beijing 100871, Peoples R China. Peking Univ, Dept Biophys, Hlth Sci Ctr, Beijing 100191, Peoples R China. Sun, F (reprint author), Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China. Sun, F (reprint author), Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China. Yin, CC (reprint author), Peking Univ, Hlth Sci Ctr, Electron Microscopy Anal Lab, Beijing 100191, Peoples R China. Sun, F (reprint author), Chinese Acad Sci, Inst Biophys, Ctr Biol Imaging, Beijing 100101, Peoples R China. Yin, CC (reprint author), Peking Univ, Ctr Prot Sci, Beijing 100871, Peoples R China. |
| Keywords | Ca2+ activation cryo-electron microscopy channel gating ion selectivity long-range allostery ryanodine receptor single-particle analysis CALCIUM-RELEASE CHANNEL MUSCLE RYANODINE RECEPTOR EM STRUCTURE DETERMINATION AMINO-ACID-RESIDUES PARTICLE CRYO-EM C-TERMINAL TAIL SKELETAL-MUSCLE SARCOPLASMIC-RETICULUM ELECTRON CRYOMICROSCOPY CARDIAC-MUSCLE |
| Issue Date | 2016 |
| Publisher | CELL RESEARCH |
| Citation | CELL RESEARCH.2016,26(9),977-994. |
| Abstract | Ryanodine receptors (RyRs) are a class of giant ion channels with molecular mass over 2.2 mega-Daltons. These channels mediate calcium signaling in a variety of cells. Since more than 80% of the RyR protein is folded into the cytoplasmic assembly and the remaining residues form the transmembrane domain, it has been hypothesized that the activation and regulation of RyR channels occur through an as yet uncharacterized long-range allosteric mechanism. Here we report the characterization of a Ca2+-activated open-state RyR1 structure by cryo-electron microscopy. The structure has an overall resolution of 4.9 angstrom and a resolution of 4.2 angstrom for the core region. In comparison with the previously determined apo/closed-state structure, we observed long-range allosteric gating of the channel upon Ca2+ activation. In-depth structural analyses elucidated a novel channel-gating mechanism and a novel ion selectivity mechanism of RyR1. Our work not only provides structural insights into the molecular mechanisms of channel gating and regulation of RyRs, but also sheds light on structural basis for channel-gating and ion selectivity mechanisms for the six-transmembrane-helix cation channel family. |
| URI | http://hdl.handle.net/20.500.11897/491441 |
| ISSN | 1001-0602 |
| DOI | 10.1038/cr.2016.99 |
| Indexed | SCI(E) PubMed 中国科技核心期刊(ISTIC) |
| Appears in Collections: | 医学部待认领 |
