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Publication Abstract from PubMed

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.

Structural basis for activity of TRIC counter-ion channels in calcium release.,Wang XH, Su M, Gao F, Xie W, Zeng Y, Li DL, Liu XL, Zhao H, Qin L, Li F, Liu Q, Clarke OB, Lam SM, Shui GH, Hendrickson WA, Chen YH Proc Natl Acad Sci U S A. 2019 Feb 15. pii: 1817271116. doi:, 10.1073/pnas.1817271116. PMID:30770441^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.