| Title | Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution |
| Authors | 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 |
| Affiliation | Tsinghua Univ, Sch Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China. Tsinghua Univ, Sch Life Sci, Ministry Educ Key Lab Prot Sci, Beijing 100084, Peoples R China. Tsinghua Univ, Sch Life Sci, Ctr Struct Biol, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China. MRC Lab Mol Biol, Cambridge CB2 0QH, England. Peking Univ, Dept Biophys, Hlth Sci Ctr, Beijing 100191, Peoples R China. Peking Univ, Ctr Prot Sci, Beijing 100191, Peoples R China. |
| Keywords | CALCIUM-RELEASE CHANNEL PARTICLE ELECTRON CRYOMICROSCOPY MUSCLE SARCOPLASMIC-RETICULUM PORE-FORMING SEGMENT SKELETAL-MUSCLE CRYO-EM CRYOELECTRON MICROSCOPY TRANSMEMBRANE DOMAINS CRYSTAL-STRUCTURES CARDIAC-MUSCLE |
| Issue Date | 2015 |
| Publisher | nature |
| Citation | NATURE.2015,517,(7532),50-+. |
| 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 organization and approximately 5,000 residues in each protomer. Here we report the structure of the rabbit RyR1 in complex with its modulator FKBP12 at an overall resolution of 3.8 angstrom, 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. A negative-charge-enriched hairpin loop connecting S5 and the pore helix 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 the membrane. Allosteric regulation of the pore by the cytoplasmic domains is mediated 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. |
| URI | http://hdl.handle.net/20.500.11897/341737 |
| ISSN | 0028-0836 |
| DOI | 10.1038/nature14063 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 医学部待认领 |
