子催化调节呼吸复合体I膜域中的质子转移反应
Hyunho Kim1, Patricia Saura1, Maximilian C Pöverlein1
1Department of Biochemistry and Biophysics, Stockholm University, Stockholm 10691, Sweden.
Journal of the American Chemical Society
|July 25, 2023
概括
复合I中的还氧反应通过远程构造变化触发了质子. 膜域中的螺旋过渡建立了质子通路,揭示了保存的合机制.
科学领域:
- 生物化学
- 分子生物学
- 结构生物学
背景情况:
- 复合物I是通过氧化化对细胞能量产生至关重要的氧化驱动质子.
- 在活性部位引发质子穿过膜的精确机制尚不完全理解.
- 最近的结构数据提供了洞察力,但缺乏远程信号的机制细节.
研究的目的:
- 阐明I复合体中氧化还原反应与质子的分子机制.
- 研究如何在子还原点的电子转移诱导着向质子释放通道传播的形状变化.
- 确定负责这种能量传导的结构元素和途径.
主要方法:
- 超过20μs的原子分子动力学 (MD) 模拟.
- 量子/经典 (QM/MM) 自由能量计算.
- 保存循环和跨膜螺旋体的形状变化的分析.
- 研究离子对的重新排列及其传播.
主要成果:
- 子还原驱动了复合I的膜结合环和螺旋体的长距离构造变化.
- 一个特定的跨膜螺旋 (TM3ND6) 经历 π → α 过渡,形成质子通路.
- 这种螺旋过渡通过湿和静电效应调节质子转移障碍.
- 一个保存的离子对和残留物网络介导来自位的信号传播.
结论:
- 在复合体I中, 反氧驱动的变形切换是质子的关键机制.
- 已识别的螺旋过渡和相关的合网络在整个复合I超级家族中得到保留.
- 由于突变导致的功能障碍可以导致严重的线粒体疾病.
- 这项研究提供了一个可概括的模型,说明催化如何驱动膜运输的大规模结构变化.
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