电压道的静止状态结构和门机制
Goragot Wisedchaisri1, Lige Tonggu2, Eedann McCord1
1Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
Cell
|July 30, 2019
概括
研究人员阐明了电压关闭 (NaV) 通道的静止状态结构,揭示了S4段运动如何控制通道关闭. 这为电压感应和激活关闭提供了一个完整的机制.
科学领域:
- 生物物理
- 结构生物学
- 分子神经科学
背景情况:
- 电压关闭的 (NaV) 通道对于刺激细胞中的电信号至关重要.
- 了解静止状态结构是阐明电压依赖的门机制的关键.
- 之前关于NaV通道休息状态的结构数据是有限的.
研究的目的:
- 确定祖先细菌道 (NaVAb) 的静止状态的冷EM结构.
- 阐明NaV通道中电压依赖的门的完整机制.
- 为电压传感器和激活门功能提供高分辨率的结构洞察力.
主要方法:
- 在 NaVAb 中进行电压转移突变和二硫化物交叉连接以稳定静止形态.
- 使用冷电子显微镜 (cryo-EM) 来获得高分辨率的结构数据.
- 分析了结构特征, 提出了详细的关门机制.
主要成果:
- 在休息状态下确定了NaVAb的冷EM结构.
- 观察到S4段的细胞内位置,与跨膜电场穿过的门电荷.
- 确定了将S4连接到S4-S5连接器的"肘部"形成,它紧了S6激活门,防止孔隙打开.
结论:
- 这种结构支持古典的
- 滑动螺旋
- 电压检测模型
- 建议采用一个完整的关门机制,包括电压传感器的移动,孔隙的打开和激活关门的关闭.
- 高分辨率结构提供了前所未有的NaV通道门动态.
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