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Structure of a Trimeric Intracellular Cation channel from C. elegans in the absence of Ca2+
Structural highlights
FunctionT38B2_CAEEL Potassium channel that mediates transmembrane potassium transport (By similarity). Might be required for maintenance of rapid intracellular calcium release (By similarity). May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores (By similarity). Binds phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:27698420).[UniProtKB:Q9DAV9][UniProtKB:Q9NA75][1] Publication Abstract from PubMedIntracellular Ca(2+) signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca(2+) from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca(2+) through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen. Genetic ablations or mutations of TRIC channels are associated with hypertension, heart disease, respiratory defects and brittle bone disease. Despite the pivotal function of TRIC channels in Ca(2+) signalling, their pore architectures and gating mechanisms remain unknown. Here we present the structures of TRIC-B1 and TRIC-B2 channels from Caenorhabditis elegans in complex with endogenous phosphatidylinositol-4,5-biphosphate (PtdIns(4,5)P2, also known as PIP2) lipid molecules. The TRIC-B1/B2 proteins and PIP2 assemble into a symmetrical homotrimeric complex. Each monomer contains an hourglass-shaped hydrophilic pore contained within a seven-transmembrane-helix domain. Structural and functional analyses unravel the central role of PIP2 in stabilizing the cytoplasmic gate of the ion permeation pathway and reveal a marked Ca(2+)-induced conformational change in a cytoplasmic loop above the gate. A mechanistic model has been proposed to account for the complex gating mechanism of TRIC channels. Pore architecture of TRIC channels and insights into their gating mechanism.,Yang H, Hu M, Guo J, Ou X, Cai T, Liu Z Nature. 2016 Oct 27;538(7626):537-541. doi: 10.1038/nature19767. Epub 2016 Oct 3. PMID:27698420[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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