在人类的Kv2.1通道中,电场诱导的孔隙收缩
Venkata Shiva Mandala1, Roderick MacKinnon1
1Laboratory of Molecular Neurobiology and Biophysics, HHMI, The Rockefeller University, New York, NY 10065.
概括
电压依赖的离子通道封锁涉及电压感应域 (VSDs),这些域将S4螺旋转移. 这种运动改变了孔状结构,根据VSD激活,道打开或关闭.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 神经科学是一个神经科学.
背景情况:
- 电压依赖的离子通道通过跨膜电压控制细胞刺激性.
- 这些通道内的电压感应域 (VSD) 将电压变化转化为形状变化.
- S4跨膜螺旋是VDS的关键组件,它介导了电压依赖的网关.
研究的目的:
- 阐明Kv2.1通道中电压依赖关的结构机制.
- 为了研究Kv2.1 VSDs在不同跨膜电压下的构造变化.
- 为了比较Kv2.1和EAG1通道的封闭机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 可视化Kv2.1结构.
- 在不同跨膜电压条件下的脂质囊中研究了Kv2.1通道.
- 结构分析的重点是S4螺旋运动及其对孔域的影响.
主要成果:
- 超极化诱导了Kv2.1 S4螺旋在1个螺旋转时~5 Å的位移.
- 观察到S4螺旋孔相互作用的变化,与通道关相关.
- 当所有四个VSD都表现出S4螺旋体位移,挤压S6螺旋体时,就发生了孔隙收缩.
结论:
- Kv2.1 S4螺旋位移直接关闭了离子通道孔.
- 部分VSD激活会使孔隙开放,而完全激活会导致狭窄.
- 尽管具有不同的架构,Kv2.1和EAG1通道共享类似的电压传感门机制.
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