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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.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1502229
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 116; Journal Issue: 10; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Wang, Xiao-hui, Su, Min, Gao, Feng, Xie, Wenjun, Zeng, Yang, Li, De-lin, Liu, Xue-lei, Zhao, Hong, Qin, Li, Li, Fei, Liu, Qun, Clarke, Oliver B., Lam, Sin Man, Shui, Guang-hou, Hendrickson, Wayne A., and Chen, Yu-hang. Structural basis for activity of TRIC counter-ion channels in calcium release. United States: N. p., 2019. Web. doi:10.1073/pnas.1817271116.
Wang, Xiao-hui, Su, Min, Gao, Feng, Xie, Wenjun, Zeng, Yang, Li, De-lin, Liu, Xue-lei, Zhao, Hong, Qin, Li, Li, Fei, Liu, Qun, Clarke, Oliver B., Lam, Sin Man, Shui, Guang-hou, Hendrickson, Wayne A., & Chen, Yu-hang. Structural basis for activity of TRIC counter-ion channels in calcium release. United States. doi:10.1073/pnas.1817271116.
Wang, Xiao-hui, Su, Min, Gao, Feng, Xie, Wenjun, Zeng, Yang, Li, De-lin, Liu, Xue-lei, Zhao, Hong, Qin, Li, Li, Fei, Liu, Qun, Clarke, Oliver B., Lam, Sin Man, Shui, Guang-hou, Hendrickson, Wayne A., and Chen, Yu-hang. Fri . "Structural basis for activity of TRIC counter-ion channels in calcium release". United States. doi:10.1073/pnas.1817271116.
@article{osti_1502229,
title = {Structural basis for activity of TRIC counter-ion channels in calcium release},
author = {Wang, Xiao-hui and Su, Min and Gao, Feng and Xie, Wenjun and Zeng, Yang and Li, De-lin and Liu, Xue-lei and Zhao, Hong and Qin, Li and Li, Fei and Liu, Qun and Clarke, Oliver B. and Lam, Sin Man and Shui, Guang-hou and Hendrickson, Wayne A. and Chen, Yu-hang},
abstractNote = {Trimeric intracellular cation (TRIC) channels are thought to provide counter-ion currents that facilitate the active release of Ca2+from intracellular stores. TRIC activity is controlled by voltage and Ca2+modulation, but underlying mechanisms have remained unknown. Here we describe high-resolution crystal structures of vertebrate TRIC-A and TRIC-B channels, both in Ca2+-bound and Ca2+-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, Ca2+binding at the luminal surface of TRIC-A, on its threefold axis, stabilizes lysine blockage of the pores. During active Ca2+release, luminal Ca2+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.},
doi = {10.1073/pnas.1817271116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 10,
volume = 116,
place = {United States},
year = {2019},
month = {2}
}

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