@article{168166,
  keywords = {Animals, Models, Molecular, Protein Structure, Tertiary, algorithms, Cryoelectron Microscopy, Rabbits, Molecular Weight, Protein Multimerization, Zinc Fingers, Ion Channel Gating, Allosteric Regulation, Ryanodine Receptor Calcium Release Channel, Sarcoplasmic Reticulum, Tacrolimus Binding Protein 1A},
  author = {Zhen Yan and Xiaochen Bai and Chuangye Yan and Jianping Wu and Zhangqiang Li and Tian Xie and Wei Peng and Changcheng Yin and Xueming Li and Sjors Scheres and Yigong Shi and Nieng Yan},
  title = {Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution},
  abstract = {<p>The ryanodine receptors (RyRs) are high-conductance intracellular Ca(2+) 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\&nbsp;{\r A}, 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.</p>
},
  year = {2015},
  journal = {Nature},
  volume = {517},
  pages = {50-55},
  month = {01/2015},
  issn = {1476-4687},
  doi = {10.1038/nature14063},
  language = {eng},
}