A two-state stabilization-change mechanism for proton-pumping complex I
A two-state stabilization-change mechanism for proton-pumping complex I
复制标题
DOI：
10.1016/j.bbabio.2011.04.006
复制
发表时间：
2011-10-01
影响因子：
4.3
通讯作者：
Brandt, Ulrich
中科院分区：
文献类型：
--
作者：
Brandt, Ulrich
尽管它在氧化磷酸化中起着重要作用，但质子泵呼吸复合物I的分子机制仍然是难以捉摸的。近年来，已经取得了相当大的进展，在这个非常大的和复杂的膜蛋白复合物的结构/功能关系的理解。去年，对细菌和线粒体复合体I的X射线晶体学分析为其分子结构提供了重要的见解。基于这一证据，在这里提出了一个假设的分子机制氧化还原驱动的质子泵的复杂I。根据该机制，两个泵模块由两个构象冲程驱动，所述两个构象冲程通过在周转期间在复合物I的外周臂中形成的半醌和泛醌醇的阴离子形式的稳定化而产生。这导致实验确定的泵浦化学计量为4 H+/2 e（-）。在两态模型中，来自铁硫团簇N2的电子转移只允许在“E-态”，而底物的质子化只可能在稳定的“P-态”。在膜臂中，从E-到P-状态的转变通过最近发现的连接两个泵模块的螺旋传输元件经由长距离构象能量转移来驱动两个泵模块。所提出的双态稳定化变化机制是完全可逆的，因此内在地解释了复合物I在正向和反向模式下的操作。这篇文章是题为呼吸道蛋白质变构协同性的特刊的一部分。(C)2011 Elsevier B. V.保留所有权利。
Despite its central function in oxidative phosphorylation, the molecular mechanism of proton pumping respiratory complex I is still elusive. In recent years, considerable progress has been made towards understanding structure/function relationships in this very large and complicated membrane protein complex. Last year X-ray crystallographic analysis of bacterial and mitochondrial complex I provided important insights into its molecular architecture. Based on this evidence, here a hypothetical molecular mechanism for redox-driven proton pumping of complex I is proposed. According to this mechanism, two pump modules are driven by two conformational strokes that are generated by stabilization of the anionic forms of semiquinone and ubiquinol that are formed in the peripheral arm of complex I during turnover. This results in the experimentally determined pumping stoichiometry of 4 H+/2e(-). In the two-state model, electron transfer from iron-sulfur cluster N2 is allowed only in the 'E-state,' while protonation of the substrate is only possible in the stabilizing 'P-state.' In the membrane arm, transition from the E- to the P-state drives the two pump modules via long range conformational energy transfer through the recently discovered helical transmission element connecting them. The proposed two-state stabilization-change mechanism is fully reversible and thus inherently explains the operation of complex I in forward and reverse mode. This article is part of a Special Issue entitled Allosteric cooperativity in respiratory proteins. (C) 2011 Elsevier B.V. All rights reserved.