激活的非选择性阴离子通道TRPM4的结构
Jiangtao Guo1,2, Ji She1,2, Weizhong Zeng1,2,3
1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA.
Nature
|December 7, 2017
概括
这项研究揭示了TRPM4通道的分子结构,TRPM4是激活的离子通道. 这些结构显示了ATP如何抑制TRPM4活动,以及它如何选择单价离子.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生理学分子生理学
背景情况:
- 暂时受体潜力美拉斯4 (TRPM4) 通道是激活的非选择性离子通道.
- TRPM4的活性是由酸丁酸-4,5-双酸盐 (PtdIns(4,5) P2) 调节的.
- 了解TRPM4的结构对于阐明其关门机制和生理作用至关重要.
研究的目的:
- 为了确定鼠标TRPM4频道的高分辨率结构.
- 为了研究ATP抑制和单价离子选择性的结构基础.
- 为TRPM频道家族的整体架构提供见解.
主要方法:
- 电子冷显微镜 (cryo-EM). 电子冷显微镜 (cryo-EM). 电子冷显微镜 (cryo-EM). 电子冷显微镜.
- 在存在或缺少ATP的情况下对TRPM4进行结构分析.
主要成果:
- 该研究介绍了小鼠TRPM4的冷EM结构,揭示了三层架构.
- ATP与N端核酸结合域结合,抑制道活动.
- 一个广泛的选择性过器,其中Gln973是关键的,确保了单价离子透性.
- S1-S4和S6后的TRP域形成了关门装置,可能会结合Ca2+和PtdIns.
结论:
- 确定的结构为TRPM4的分子架构提供了基本的理解.
- 这些发现对于破译TRPM4.的复杂门机制至关重要.
- 这项研究为TRPM4的离子选择性和由ATP和脂质调节提供了结构基础.
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