在3.6 Å的分辨率下,电压通道Ca(v) 1.1的结构
Jianping Wu1,2,3, Zhen Yan1,2, Zhangqiang Li1,2,3
1State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
Nature
|September 1, 2016
概括
我们确定了子Cav1.1通道的冷-EM结构, 结构显示了潜在的无活化状态,提供了对激发-收缩合机制的洞察.
科学领域:
- 结构生物学
- 分子生理学
- 生物物理
背景情况:
- 电压通道 (Cav) 对于细胞信号传递至关重要,将电刺激转化为细胞内 (Ca2+) 事件.
- Cav1.1 是负责骨肌肉激发-收缩合的特定亚型.
研究的目的:
- 确定子Cav1.1复合物的高分辨率冷电子显微镜 (冷EM) 结构.
- 阐明骨肌肉激发-收缩合中的Cav1.1功能的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得子Cav1.1复合物的结构.
- 粒子分类产生了多个重建,包括附加状态的移动子单元.
主要成果:
- 3.6 Å的分辨率结构显示了Cav1.1内门封闭和电压感应领域的"上升"形状,表明了无活化状态.
- 孔域,细胞外环和子单元相互作用 (α2δ-1,β1a) 的详细特征得到解决.
- 重建显示了涉及β1a子单元的动态重组.
结论:
- 原子模型的Cav1.1提供了理解骨肌肉激发-收缩合的结构基础.
- 该结构作为解释Cav和Nav通道的功能和疾病机制的模板.
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