Structural basis for activity of TRIC counter-ion channels in calcium release

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, Yu hang Chen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4238-4243
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number10
DOIs
StatePublished - 2019

Keywords

  • Ca modulation
  • Counter-ion mechanism
  • Electrophysiology
  • Lipid modulation
  • X-ray crystallography

ASJC Scopus subject areas

  • General

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