@article{9793872846f94a77a1573a51fe997841,
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.",
author = "Wei Peng and Huaizong Shen and Jianping Wu and Wenting Guo and Xiaojing Pan and Ruiwu Wang and Chen, {S. R.Wayne} and Nieng Yan",
note = "Funding Information: We thank J. Lei and X. Li for technical support. We thank the Tsinghua University Branch of the China National Center for Protein Sciences (Beijing) for providing facility support. The computation was completed on the {"}Explorer 100{"} cluster system of Tsinghua National Laboratory for Information Science and Technology. This work was supported by funds from the Ministry of Science and Technology of China (2015CB9101012014, 2016YFA0500402, and ZX09507003006), the National Natural Science Foundation of China (project 31321062), the Canadian Institutes of Health Research (MOP-123506 to S.R.W.C), and the Heart and Stroke Foundation of Canada (G-16-00014214 to S.R.W.C). W.G. was supported by the Alberta Innovates-Health Solutions Graduate Studentship Award. S.R.W.C. is an Alberta Innovates-Health Solutions Scientist and was supported in part by the Heart and Stroke Foundation/Libin Cardiovascular Institute Professorship in Cardiovascular Research. The research of N.Y. was supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institute and an endowed professorship from Bayer Healthcare. The atomic coordinates of pRyR2 in the closed and open states have been deposited in the Protein Data Bank with the accession codes 5GO9 and 5GOA, respectively. The corresponding maps have been deposited in the Electron Microscopy Data Bank with the accession codes EMD-9528 and EMD-9529, respectively.",
year = "2016",
month = oct,
day = "21",
doi = "10.1126/science.aah5324",
language = "English (US)",
volume = "354",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6310",
}