两个孔域K道TASK2的pH门的结构基础
Baobin Li1,2,3, Robert A Rietmeijer1,2,3,4, Stephen G Brohawn5,6,7
1Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.
Nature
|October 1, 2020
概括
TASK2通道控制细胞刺激性和pH平衡. 新的结构揭示了两个不同的pH感应门,一个细胞内和一个细胞外,解释了质子如何调节TASK2通道活性.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 生理学 生理学 生理学
背景情况:
- 塔斯克2 (KCNK5) 通道是pH值关闭的通道,对细胞电刺激性至关重要.
- 它们在调节呼吸和维持脏pH平衡中起着至关重要的作用.
- 在TASK2通道中依赖pH的门的精确机制仍然未被阐明.
研究的目的:
- 确定TASK2通道中的pH依赖门的结构基础.
- 阐明由细胞内和细胞外pH控制的独特封闭机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得高分辨率的Mus musculus结构 TASK2.2.
- 在脂质纳米盘中确定了开放式和封闭式通道构造的结构.
- 分子分析的重点是确定关键的残留物和关所涉及的形状变化.
主要成果:
- 确定了两种新的封闭机制,与以前已知的通道门不同.
- 细胞内关涉及氨酸残留物在内部螺旋体上的质子化,形成细胞质密封.
- 细胞外关涉及氨酸残留的质子化和影响选择性波器的形状变化.
结论:
- 该研究揭示了TASK2通道中的双门系统,对膜两侧的pH值变化作出反应.
- 特定残留物 (氨酸和氨酸) 的质子化是显著的细胞内和细胞外隔离机制的基础.
- 这些发现为TASK2通道如何感知和响应pH值变化以调节离子流提供了机制性的解释.
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