Respiratory complex I is a redox-driven proton pump. Several high-resolution structures of complex I have been determined providing important information about the putative proton transfer paths and conformational transitions that may occur during catalysis. However, how redox energy is coupled to the pumping of protons remains unclear. In this article, we review biochemical, structural and molecular simulation data on complex I and discuss several coupling models, including the key unresolved mechanistic questions. Focusing both on the quinone-reductase domain as well as the proton-pumping membrane-bound domain of complex I, we discuss a molecular mechanism of proton pumping that satisfies most experimental and theoretical constraints. We suggest that protonation reactions play an important role not only in catalysis, but also in the physiologically-relevant active/deactive transition of complex I.

中文翻译：

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呼吸复合物 I 中的长程电子质子耦合——来自醌室和反向转运蛋白样亚基的分子模拟的见解

呼吸复合体 I 是氧化还原驱动的质子泵。复合物 I 的几种高分辨率结构已被确定，提供了有关催化过程中可能发生的推定质子转移路径和构象转变的重要信息。然而，氧化还原能量如何与质子泵浦耦合仍不清楚。在本文中，我们回顾了复合物 I 的生化、结构和分子模拟数据，并讨论了几种耦合模型，包括尚未解决的关键机制问题。我们重点关注复合物 I 的醌还原酶结构域和质子泵浦膜结合结构域，讨论了满足大多数实验和理论限制的质子泵浦分子机制。我们认为质子化反应不仅在催化中发挥着重要作用，而且在复合物 I 的生理相关活性/失活转变中也发挥着重要作用。