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人类TRPM4离子通道在脂质纳米盘中的结构

Henriette E Autzen^1,2, Alexander G Myasnikov¹, Melody G Campbell¹

¹Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.

Science (New York, N.Y.)

|December 9, 2017

概括

TRPM4通道的结构揭示了它的架构和结合部位. 与短暂受体潜力美拉斯4 (TRPM4) 通道的结合导致了形状变化,为电压依赖的开放做了准备.

科学领域:

结构生物学结构生物学
离子通道生理学离子通道生理学
心血管研究研究心血管研究

背景情况:

暂时受体潜能拉斯4 (TRPM4) 是一种子通道,与心血管疾病有关.
TRPM4的激活取决于细胞内和电压,具有独特的单价离子透性.

研究的目的:

为了确定全身人类TRPM4.4的高分辨率结构.
为了阐明TRPM4依赖的门的结构基础.

主要方法:

单粒子冷电子显微镜 (冷电子显微镜)
脂质纳米光盘技术的技术
在~3-angstrom分辨率下确定结构.

主要成果:

解决了人类TRPM4的两个不同的封闭状态结构.
在细胞内S1-S4域中确定了一个明确的结合部位.
结合会诱导道的形状变化.

结论:

确定的结构为TRPM4通道子家族的架构提供了洞察力.
结合可能将TRPM4原始化为随后的电压依赖开放.
这些发现提升了对心血管生理学中TRPM4功能的理解.

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