Structural basis for activity of TRIC counter-ion channels in calcium release
| Autor: | Xue lei Liu, Li Qin, Guanghou Shui, Wayne A. Hendrickson, Fei Li, Yang Zeng, Qun Liu, Sin Man Lam, Xiaohui Wang, Min Su, De lin Li, Wenjun Xie, Feng Gao, Yu-hang Chen, Oliver B. Clarke, Hong Zhao |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular 0301 basic medicine Cytoplasm Protein Conformation chemistry.chemical_element Protomer Calcium Crystallography X-Ray Ion Channels 03 medical and health sciences 0302 clinical medicine Sequence Analysis Protein Cations Animals Calcium Signaling Diacylglycerol kinase Multidisciplinary Conductance Membrane hyperpolarization Biological Sciences Electrophysiology 030104 developmental biology chemistry Mutagenesis Helix Biophysics sense organs 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Proceedings of the National Academy of Sciences. 116:4238-4243 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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