微秒分子模拟揭示了中的过渡性质子路径
L Michel Espinoza-Fonseca1, G Lizbeth Ramírez-Salinas2
1†Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Journal of the American Chemical Society
|June 2, 2015
概括
肉质网膜Ca2+-ATPase (SERCA) 在快速结构变化过程中使用过渡性质子通路. 这种途径优化运输,并通过中和充电点来保持的稳定性.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 膜运输 运输 膜运输
背景情况:
- 肉质网膜Ca2+) -ATPase (SERCA) 对于肌肉收缩至关重要,运输Ca2+) 和H2+) 离子.
- 为了保持结构完整,SERCA使用单独的离子运输途径来保持结构完整.
- 在快速结构转换过程中,是否存在同步的离子通路仍然不清楚.
研究的目的:
- 在SERCA中的快速 (微秒) 结构转换过程中研究同时存在的质子和金属离子路径的存在和功能.
- 为了阐明在快速的SERCA形状变化过程中质子运输的机制.
主要方法:
- 对一个质子化的SERCA中间体 (E1·H(+) 771) 的微秒长分子动力学轨迹的分析.
- 使用结构分析识别和表征短暂的疏水孔.
- 蛋白质pKa计算,以评估孔隙对质子运输的适用性.
主要成果:
- 在6号,8号和9号跨膜螺旋的光侧发现了一个短暂的疏水孔.
- 这个孔隙通过水分子将运输部位连接到光层,从而促进质子运输.
- 孔隙适合质子运输,这是结构分析和pKa计算表明的.
结论:
- 在SERCA中存在一个短暂的质子通路,在快速结构转换期间活跃.
- 这条路径中和了运输站点,保持了SERCA的稳定性,并优化了Ca2+) 运输.
- 这些发现提供了通过短暂的疏水孔透过P型ATPases的离子交换机制的见解.
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