在原型质子通道中的多个时间尺度上运输相关的蛋白质构造动力学和水动力学:固态NMR的洞察
Venkata S Mandala1, Martin D Gelenter1, Mei Hong1
1Department of Chemistry, Massachusetts Institute of Technology , 170 Albany Street, Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|January 6, 2018
概括
流感M2蛋白质
科学领域:
- 生物物理
- 结构生物学
- 膜蛋白质
背景情况:
- 流感M2蛋白形成一个四重质子通道,对于病毒的进入至关重要.
- 之前的研究已经确定了histidine在质子转移中的作用, 但无法解释缓慢的导电率.
- M2 蛋白质表现出形状可塑性,表明动力学影响功能.
研究的目的:
- 使用固态NMR研究M2蛋白的W41F突变.
- 阐明质子导电率与分子动力学之间的差异.
- 连接蛋白质和水的动态与质子导电机制.
主要方法:
- 在M2蛋白W41F突变体上进行固态NMR光谱.
- 化学转移分析以确定形状.
- 放松测量以探测水动力学.
- 用二维相关谱测定相互转换率.
主要成果:
- 根据pH值确定了两种不同的四聚体构造.
- 在~400s-1之间观察到的相互转换,与运输时间尺度相关.
- 运河水表现出纳秒运动, 独立于pH值.
- 确定了水运动,胺转移和形状变化的不同时间尺度.
结论:
- 质子传导涉及格罗特斯跳跃 (皮秒-纳米秒的水运动).
- 希斯提丁侧链动态 (微秒) 促进了水-希斯提丁质子转移.
- 限制速度的步骤是四螺旋束运动 (毫秒),控制质子流.
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