Conformation-driven and semiquinone-gated proton-pump mechanism in the NADH-ubiquinone oxidoreductase (complex I)
Conformation-driven and semiquinone-gated proton-pump mechanism in the NADH-ubiquinone oxidoreductase (complex I)
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DOI：
10.1016/j.febslet.2005.06.086
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发表时间：
2005-08-29
期刊：
影响因子：
3.5
通讯作者：
Salerno, JC
中科院分区：
文献类型：
--
作者：
Ohnishi, T;Salerno, JC
基于以下发现，提出了nadh -醌氧化还原酶（复合物1）的质子/电子转移新机制：(1)结合蛋白的快速弛弛性半醌阴离子自由基（简称Q(Nf)）的EPR信号(；-))只有在质子-跨膜电化学电位存在时才能观察到；(2)铁硫簇N2和Q（Nf）。-)，是直接自旋耦合的；(3)胞间旋载体的投影仅沿膜正常延伸5 [Yano， T., Dunham， W.R. and Ohnishi， T.（2005）生物化学，44,1744-1754]。我们提出质子泵是由氧化还原驱动的醌结合蛋白的构象变化来操作的。在输入状态下，半醌被还原为醌，从线粒体内膜的N（基质）侧获得两个质子，从呼吸链的低电位（NADH）侧获得一个电子。构象变化使质子通过质子阱在膜的P（膜间空间）一侧释放。同时，在偶联位点的高电位侧，一个电子被捐赠给醌池。然后系统返回到原始状态，重复这个循环。这一假设为进一步研究复合体i中质子易位的机制提供了一个有用的框架。Elsevier B.V.版权所有。
A novel mechanism for proton/electron transfer is proposed for NADH-quinone oxidoreductase (complex 1) based on the following findings: (1) EPR signals of the protein-bound fast-relaxing semiquinone anion radicals (abbreviated as Q(Nf)(.-)) are observable only in the presence of proton-transmembrane electrochemical potential; (2) Iron-sulfur cluster N2 and Q(Nf)(.-), are directly spin-coupled; and (3) The projection of the interspin vector extends only 5 along the membrane normal [Yano, T., Dunham, W.R. and Ohnishi, T. (2005) Biochemistry, 44,1744-1754].We propose that the proton pump is operated by redox-driven conformational changes of the quinone binding protein. In the input state, semiquinone is reduced to quinol, acquiring two protons from the N (matrix) side of the mitochondrial inner membrane and an electron from the low potential (NADH) side of the respiratory chain. A conformational change brings the protons into position for release at the P (inter-membrane space) side of the membrane via a proton-well. Concomitantly, an electron is donated to the quinone pool at the high potential side of the coupling site. The system then returns to the original state to repeat the cycle. This hypothesis provides a useful frame work for further investigation of the mechanism of proton translocation in complex I. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.