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现在位置:首页 > 科研进展 > 最新重要论文(影响因子PNAS及以上)
Pore architecture of TRIC channels and insights into their gating mechanism, Nature(2016), Published online 03 October 2016
2016-10-10 | 【     】【打印】【关闭

Nature(2016), Published online 03 October 2016, doi:10.1038/nature19767

Pore architecture of TRIC channels and insights into their gating mechanism

Hanting Yang, Miaohui Hu, Jianli Guo, Xiaomin Ou, Tanxi Cai & Zhenfeng Liu

Abstact

Intracellular Ca2+ signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis1, 2. Release of Ca2+ from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER)3, 4. Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca2+ through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen5, 6. Genetic ablations or mutations of TRIC channels are associated with hypertension, heart disease, respiratory defects and brittle bone disease7, 8, 9, 10, 11, 12. Despite the pivotal function of TRIC channels in Ca2+ signalling5, 13, 14, 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 Ca2+-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.

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201610/t20161004_4672688.html

文章链接: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature19767.html

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