title: Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2.
abstract: RyR2 is a high-conductance intracellular calcium (Ca2+) channel that controls the release of Ca2+from the sarco(endo)plasmic reticulum of a variety of cells. Here, we report the structures of RyR2 from porcine heart in both the open and closed states at near-atomic resolutions determined using single-particle electron cryomicroscopy. Structural comparison reveals a breathing motion of the overall cytoplasmic region resulted from the interdomain movements of amino-terminal domains (NTDs), Helical domains, and Handle domains, whereas almost no intradomain shifts are observed in these armadillo repeats-containing domains. Outward rotations of the Central domains, which integrate the conformational changes of the cytoplasmic region, lead to the dilation of the cytoplasmic gate through coupled motions. Our structural and mutational characterizations provide important insights into the gating and disease mechanism of RyRs.
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.|Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Huaizong
authors.initials: H
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.|Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.affiliation: The Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada, T2N 4N1.
authors.forename: Wenting
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Pan
authors.affiliation: The Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada, T2N 4N1.
authors.forename: Ruiwu
authors.initials: R
authors.lastname: Wang
authors.affiliation: The Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada, T2N 4N1. swchen@ucalgary.ca nyan@tsinghua.edu.cn.
authors.forename: S R Wayne
authors.initials: SR
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. swchen@ucalgary.ca nyan@tsinghua.edu.cn.|Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.|Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Nieng
authors.initials: N
authors.lastname: Yan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020285:Cryoelectron Microscopy; D003593:Cytoplasm / Q000737:chemistry; D006321:Heart; D015640:Ion Channel Gating; D009154:Mutation; D000072417:Protein Domains; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D013552:Swine
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium