@article{453af997a4ae40e6981725057de2c52e,
title = "Structural basis for activity of TRIC counter-ion channels in calcium release",
abstract = " Trimeric intracellular cation (TRIC) channels are thought to provide counter-ion currents that facilitate the active release of Ca 2+ from intracellular stores. TRIC activity is controlled by voltage and Ca 2 + modulation, but underlying mechanisms have remained unknown. Here we describe high-resolution crystal structures of vertebrate TRIC-A and TRIC-B channels, both in Ca 2+ -bound and Ca 2+ -free states, and we analyze conductance properties in structure-inspired mutagenesis experiments. The TRIC channels are symmetric trimers, wherein we find a pore in each protomer that is gated by a highly conserved lysine residue. In the resting state, Ca 2 + binding at the luminal surface of TRIC-A, on its threefold axis, stabilizes lysine blockage of the pores. During active Ca 2+ release, luminal Ca 2+ depletion removes inhibition to permit the lysine-bearing and voltage-sensing helix to move in response to consequent membrane hyperpolarization. Diacylglycerol is found at interprotomer interfaces, suggesting a role in metabolic control.",
keywords = "Ca modulation, Counter-ion mechanism, Electrophysiology, Lipid modulation, X-ray crystallography",
author = "Wang, {Xiao hui} and Min Su and Feng Gao and Wenjun Xie and Yang Zeng and Li, {De lin} and Liu, {Xue lei} and Hong Zhao and Li Qin and Fei Li and Qun Liu and Clarke, {Oliver B.} and Lam, {Sin Man} and Shui, {Guang hou} and Hendrickson, {Wayne A.} and Chen, {Yu hang}",
note = "Funding Information: We thank Bailong Xiao, Jie Geng, and Qi Yuan for helpful discussions and initiating preliminary lipid bilayer experiments; Yanan Deng and Meihua Wang for help with protein chemistry and crystallography; and Wen-ming Qin, De-qiang Rao, and Raj Surajit for help with synchrotron experiments at various beamlines, including BL19U and BL17U at the Shanghai Synchrotron Radiation Facility and 24-IDC at the Advanced Photon Source. This project is financially supported by National Key R&D Program of China Grants 2016YFA0500503 and 2015CB910102; Chinese Academy of Sciences Strategic Priority Research Program XDB08020301; and National Natural Science Foundation of China Grants 31872721, 31470728, and 31322005 (to Y.-h.C.), 31728010 (to Y.-h.C. and F.L.), and 11672226 (to W.X.). Y.-h.C. is supported in part by the National Thousand Young Talents program from the Office of Global Experts Recruitment in China. W.X. is supported in part by the Young Talent Support Plan of Xi{\textquoteright}an Jiao-tong University and State Key Laboratory of Molecular Developmental Biology, China Grant 2018-MDB-KF-02. F.L. is supported in part by NIH Grant R01GM106037. W.A.H. is supported in part by NIH Grant GM 107462. This work was also benefited from NIH support to the Center on Membrane Protein Production and Analysis (COMPP{\AA}, Grant P41 GM116799). Funding Information: ACKNOWLEDGMENTS. We thank Bailong Xiao, Jie Geng, and Qi Yuan for helpful discussions and initiating preliminary lipid bilayer experiments; Yanan Deng and Meihua Wang for help with protein chemistry and crystallography; and Wen-ming Qin, De-qiang Rao, and Raj Surajit for help with synchrotron experiments at various beamlines, including BL19U and BL17U at the Shanghai Synchrotron Radiation Facility and 24-IDC at the Advanced Photon Source. This project is financially supported by National Key R&D Program of China Grants 2016YFA0500503 and 2015CB910102; Chinese Academy of Sciences Strategic Priority Research Program XDB08020301; and National Natural Science Foundation of China Grants 31872721, 31470728, and 31322005 (to Y.-h.C.), 31728010 (to Y.-h.C. and F.L.), and 11672226 (to W.X.). Y.-h.C. is supported in part by the National Thousand Young Talents program from the Office of Global Experts Recruitment in China. W.X. is supported in part by the Young Talent Support Plan of Xi{\textquoteright}an Jiao-tong University and State Key Laboratory of Molecular Developmental Biology, China Grant 2018-MDB-KF-02. F.L. is supported in part by NIH Grant R01GM106037. W.A.H. is supported in part by NIH Grant GM 107462. This work was also benefited from NIH support to the Center on Membrane Protein Production and Analysis (COMPP{\AA}, Grant P41 GM116799). Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All Rights Reserved.",
year = "2019",
doi = "10.1073/pnas.1817271116",
language = "English (US)",
volume = "116",
pages = "4238--4243",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "10",
}