PNAS
Abstract
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.
| 论文编号: | DOI:10.1073/pnas.1817271116 |
| 论文题目: | Structural basis for activity of TRIC counter-ion channels in calcium release |
| 英文论文题目: | Structural basis for activity of TRIC counter-ion channels in calcium release |
| 第一作者: | Xiao-hui Wang, Min Su, Feng Gao, Wenjun Xie, Yang Zeng, De-lin Li, Xue-lei Liu, Hong Zhao, Li Qin, Fei Li, Qun Liu, Oliver B. Clarke, Sin Man Lam, Guang-hou Shui, Wayne A. Hendrickson, and Yu-hang Chen |
| 英文第一作者: | Xiao-hui Wang, Min Su, Feng Gao, Wenjun Xie, Yang Zeng, De-lin Li, Xue-lei Liu, Hong Zhao, Li Qin, Fei Li, Qun Liu, Oliver B. Clarke, Sin Man Lam, Guang-hou Shui, Wayne A. Hendrickson, and Yu-hang Chen |
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| 发表年度: | 2019-02-19 |
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| 摘要: | 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. |
| 英文摘要: | 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. |
| 刊物名称: | PNAS |
| 英文刊物名称: | PNAS |
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| 其它备注: | Xiao-hui Wang, Min Su, Feng Gao, Wenjun Xie, Yang Zeng, De-lin Li, Xue-lei Liu, Hong Zhao, Li Qin, Fei Li, Qun Liu, Oliver B. Clarke, Sin Man Lam, Guang-hou Shui, Wayne A. Hendrickson, and Yu-hang Chen. Structural basis for activity of TRIC counter-ion channels in calcium release. PNAS. DOI:10.1073/pnas.1817271116 |
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