对通道电压传感器停机状态的结构预测
Michael Grabe1, Helen C Lai, Monika Jain
1Department of Physiology, Howard Hughes Medical Institute.
Nature
|December 26, 2006
概括
通道中的电压感应域 (VSD) 在电压封闭过程中经历了显著的重组. 这项研究揭示了VSD跨膜包装在非导电的.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 生物物理学的生物物理.
- 结构生物学 结构生物学
背景情况:
- 电压关闭 (Kv) 通道通过电压感应域 (VSD) 的结构变化调节离子运输和细胞刺激性.
- 对于通道封锁至关重要的VDS的"下降状态"形状以及S4段的精确运动仍然不太清楚.
- 现有的结构数据,如Kv1.2,主要代表"上位状态",在理解非导电状态时留下了一个差距.
研究的目的:
- 为了阐明VSDs在KV通道的非导电"下降状态"中的跨膜包装.
- 为了确定在电压封闭过程中VDS的结构重排.
- 为VDS在其下置状态提供一个结构模型.
主要方法:
- 使用了带有条件致死性/第二位抑制剂酵母幕,其中具有真核细胞KV通道KAT1.1.
- 在KAT1中引入了条件致命突变,并确定了恢复酵母生长的抑制器突变.
- 使用相互作用的残留约束和工程抑制器突变构建和验证了一个下降状态的VSD模型.
主要成果:
- 确定了VSD在下置状态下的特定的跨膜包装安排.
- 基于实验约束,在下置状态下开发了Kv通道VSD的结构模型.
- 在封闭时显示出大量的VSD重排,S4段与孔相对保持一致的位置.
结论:
- 在电压封闭过程中,VSD会经历显著的形状变化.
- 在上下两种状态之间,S4段的位置被保留,这表明它在通道功能中起着保留的作用.
- 生成的下降状态模型为KV通道封闭机制提供了关键的见解.
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