电压关闭的K+通道Eg1的结构显示出一种替代的电压传感机制
Jonathan R Whicher1, Roderick MacKinnon2
1Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
哺乳动物K(v) 10.1 (Eag1) 通道的结构显示出一种新的电压依赖的门机制. 卡尔莫杜林与S4 - S5链接器结合,使孔关闭,而不影响电压传感器的位置.
科学领域:
- 生物物理
- 结构生物学
- 分子生理学
背景情况:
- 电压通道调节细胞刺激能力.
- 网格通常由通过S4-S5链接器连接到孔隙的电压传感器进行介导.
- K(v) 10.1 (Eag1) 道是一个独特的子家族,具有独特的封闭性质.
研究的目的:
- 确定哺乳动物的K10.1 (Eag1) 通道的高分辨率结构.
- 阐明Eag1通道封闭和calmodulin抑制的结构基础.
- 在K (v) 道中研究潜在的替代道机制.
主要方法:
- 单粒子冷电子显微镜 (冷EM).
- 在3.78安格斯特罗姆分辨率下确定Eag1-calmodulin复合结构.
主要成果:
- Eag1 结构显示出一个明显的 S4-S5 连接器作为五个残留循环.
- 跨膜段没有域互换,不同于其他K(v) 道结构.
- 卡尔莫杜林与细胞内域结合,独立于电压传感器位置关闭孔隙.
结论:
- 根据Eag1结构,在Kv通道中采用了电压依赖的门的替代机制.
- 独特的S4-S5链接器和calmodulin相互作用提供了对Eag1通道调节的见解.
- 这项工作提供了一个理解Eag1和相关通道门的结构模板.
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