Department of Physics, University of Helsinki, Finland.
Institute of Biochemistry II, University Hospital, Goethe University, Frankfurt am Main, Germany.
FEBS Lett. 2022 May;596(9):1133-1146. doi: 10.1002/1873-3468.14346. Epub 2022 Apr 17.
The first component of the mitochondrial electron transport chain is respiratory complex I. Several high-resolution structures of complex I from different species have been resolved. However, despite these significant achievements, the mechanism of redox-coupled proton pumping remains elusive. Here, we combined atomistic docking, molecular dynamics simulations, and site-directed mutagenesis on respiratory complex I from Yarrowia lipolytica to identify a quinone (Q)-binding site on its surface near the horizontal amphipathic helices of ND1 and NDUFS7 subunits. The surface-bound Q makes stable interactions with conserved charged and polar residues, including the highly conserved Arg72 from the NDUFS7 subunit. The binding and dynamics of a Q molecule at the surface-binding site raise interesting possibilities about the mechanism of complex I, which are discussed.
线粒体电子传递链的第一个组成部分是呼吸复合物 I。已经解析了来自不同物种的几种高分辨率的复合物 I 结构。然而，尽管取得了这些重大成就，氧化还原偶联质子泵的机制仍然难以捉摸。在这里，我们结合了来自酿酒酵母的呼吸复合物 I 的原子对接、分子动力学模拟和定点突变，鉴定了其表面上靠近 ND1 和 NDUFS7 亚基水平的两亲性螺旋的醌 (Q)-结合位点。表面结合的 Q 与保守的带电和极性残基稳定相互作用，包括 NDUFS7 亚基中高度保守的 Arg72。在表面结合位点上 Q 分子的结合和动态提出了关于复合物 I 机制的有趣可能性，对此进行了讨论。
