人类电压门式质子通道的内部pH感应残留物Hv1是histidine 168
Mingzhe Shen1, Yandong Huang2, Zhitao Cai2
1Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland.
Biophysical journal
|July 26, 2024
概括
研究人员确定Histidine 168 (H168) 是人类电压门式质子通道 (hHv1) 中的关键pH传感器. 它的质子化状态通过影响螺旋体运动来影响通道开放,揭示了对pH依赖性门的洞察力.
科学领域:
- 生物物理学的生物物理.
- 分子生物学分子生物学
- 离子通道生理学 离子通道生理学
背景情况:
- 人类的电压门式质子通道 (hHv1) 在细胞pH稳态和生物能量学中起着至关重要的作用.
- 控制hHv1关口的精确分子机制,特别是它的pH敏感性,尚未完全理解.
研究的目的:
- 用先进的计算模拟来研究hHv1的pH感应机制.
- 为了确定道对pH值变化的反应中涉及的特定残留物,并将它们的质子化状态与道构造过渡联系起来.
主要方法:
- 膜启用混合溶剂连续恒定pH分子动力学 (CpHMD) 模拟.
- 采用pH复制交换技术来探索各种质子化状态.
- 在封闭和开放通道状态之间的过渡期间分析结构变化和残留质子化.
主要成果:
- 三种残留物被确定为能够在通道脱极化过程中获得或失去质子.
- 位于S3螺旋的细胞内末端的168 (H168) 被发现在通道开通时从去质子化转换为质子化.
- H168质子与增加的S3螺旋倾斜和增强的S4螺旋移动性相关,表明在通道关中发挥了作用.
结论:
- 提议用histidine 168 (H168) 作为一个关键的细胞内pH传感器,用于hH1.
- H168的质子化可能会充当分子开关,通过调节螺旋动力学来启动通道打开.
- 这项研究为hHv1通道的pH依赖性关机制提供了重要的见解.
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