人类TRPM4通道的电子冷显微镜结构
Paige A Winkler1, Yihe Huang1, Weinan Sun2
1Van Andel Institute, 333 Bostwick Avenue N.E., Grand Rapids, Michigan 49503, USA.
Nature
|December 7, 2017
概括
研究人员可视化了TRPM4通道的结构,该通道对细胞信号传递至关重要. 这为激活非选择性 (CAN) 通道的功能提供了新的见解,并可以为药物开发提供信息.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 结构生物学 结构生物学
背景情况:
- 激活的非选择性 (CAN) 离子通道调节细胞的进入.
- 这些通道对于神经元爆发和心脏节律至关重要.
- TRPM4是CAN通道家族中广泛和重要的成员.
研究的目的:
- 为了确定人类TRPM4通道的结构.
- 了解 (Ca2+) 和甲卡瓦纳与TRPM4的结合.
- 阐明CAN和TRPM通道的功能和药理性质.
主要方法:
- 使用电子冷显微镜 (cryo-EM) 可视化TRPM4通道结构.
- 结构在激动剂Ca2+和调节剂decavanadate的存在下确定.
主要成果:
- 该结构显示出由四个TRPM4子单元组成的冠状结构.
- 细胞质C端域形成了一个类似的结构.
- 确定了两个decavanadate结合位点,一个在C端域,另一个在MHR跨子单元接口.
- 选择性过器中的谷氨胺残留物可能决定单价离子选择性.
结论:
- 确定的结构为TRPM4道功能提供了新的见解.
- 这些结构信息可以促进对CAN和TRPM通道家族的理解.
- 这些发现可能会指导未来对这些离子通道的药理学向.
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