来自电的Nav1.4-β1复合物的结构
Zhen Yan1, Qiang Zhou1, Lin Wang1
1State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China; Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
Cell
|July 25, 2017
概括
我们确定了电盐道 (Nav) 的冷-EM结构及其β1子单位. 这显示了道如何
科学领域:
- 结构生物学
- 神经科学
- 生物物理
背景情况:
- 电压通道 (Nav) 对于刺激细胞中的电信号至关重要.
- 了解Nav通道结构是解读动作潜能生成和传播的关键.
- 之前的结构研究已经提供了对封闭状态的洞察力,但对开放状态的理解仍然较少.
研究的目的:
- 确定电Nav1.4通道 (EeNav1.4) 与β1子单元复合的冷电子显微镜 (冷EM) 结构.
- 阐明通道封闭和快速失活的结构基础.
- 提供对动力潜力的传播机制的见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定与β1亚单元复合的EeNav1. 4的结构.
- 在4.0 Å分辨率的高分辨率结构分析.
- 与先前确定的封闭Nav通道结构进行比较的结构分析.
主要成果:
- 与β1亚单元的EeNav1.4的冷EM结构在4.0 Å分辨率下得到解析.
- 该β1子单元的免疫球蛋白域与细胞外环相互作用,其跨膜螺旋接触电压感应域III (VSDIII).
- 电压感应域处于"上"形状,表示开放状态,细胞内门由类似于数字的分子保持开放.
- 结构比较显示了门电荷转移和孔隙扩张之间的合,涉及多个通道段.
- 负责快速失活的IFM动机位于III和IV重复中,这表明有异质阻断机制.
结论:
- 确定结构提供了电压门通道的开放状态的高分辨率快照.
- β1子单元的相互作用会影响通道的关闭和稳定性.
- 这些发现阐明了快速无活化和孔隙开放的机制,为治疗干预提供了目标.
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