Architecture of complex I and its implications for electron transfer and proton pumping.
Architecture of complex I and its implications for electron transfer and proton pumping.
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DOI：
10.1016/j.bbabio.2009.01.012
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发表时间：
2009-06
影响因子：
4.3
通讯作者：
Brandt, Ulrich
中科院分区：
文献类型：
--
作者：
Zickermann, Volker;Kerscher, Stefan;Zwicker, Klaus;Tocilescu, Maja A.;Radermacher, Michael;Brandt, Ulrich
关键词：
质子泵NADH：泛醌氧化还原酶（复合物I）是呼吸链中最大的，也是迄今为止了解最少的酶复合物。它由一个周边臂窝藏所有已知的氧化还原活性辅基和一个膜臂与一个尚未未知数量的质子易位位点。泛醌还原位点接近铁硫簇N2的49-kDa和PSST亚基的接口已被映射通过广泛的定点诱变。独立的证据表明，泛醌还原过程中的电子转移事件与电位下降有关，电位下降产生了4 H+/2 e −化学计量的质子移位的全部驱动力。免疫标记的天然酶和缺乏电子输入模块的亚复合物的电子显微镜分析表明，N2簇到膜表面的距离为35-60 μ m。分解成亚复合物的膜臂表明，即使是远端部分也含有亚基，这些亚基是参与质子易位的主要候选者，因为它们与钠/质子反向转运蛋白同源，并且在预测的跨膜螺旋中含有保守的带电残基。通过复合物I的氧化还原连接的质子易位的机制在很大程度上是未知的，但必须包括能量在极长距离上传输的步骤。在这篇综述中，我们汇编了有关复杂I的结构信息，并讨论了复杂I功能的影响。
Proton pumping NADH:ubiquinone oxidoreductase (complex I) is the largest and remains by far the least understood enzyme complex of the respiratory chain. It consists of a peripheral arm harbouring all known redox active prosthetic groups and a membrane arm with a yet unknown number of proton translocation sites. The ubiquinone reduction site close to iron-sulfur cluster N2 at the interface of the 49-kDa and PSST subunits has been mapped by extensive site directed mutagenesis. Independent lines of evidence identified electron transfer events during reduction of ubiquinone to be associated with the potential drop that generates the full driving force for proton translocation with a 4 H+/2e− stoichiometry. Electron microscopic analysis of immuno-labelled native enzyme and of a subcomplex lacking the electron input module indicated a distance of 35–60 Å of cluster N2 to the membrane surface. Resolution of the membrane arm into subcomplexes showed that even the distal part harbours subunits that are prime candidates to participate in proton translocation because they are homologous to sodium/proton antiporters and contain conserved charged residues in predicted transmembrane helices. The mechanism of redox linked proton translocation by complex I is largely unknown but has to include steps where energy is transmitted over extremely long distances. In this review we compile the available structural information on complex I and discuss implications for complex I function.
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