A Structural Perspective on Respiratory Complex I

A Structural Perspective on Respiratory Complex I
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呼吸复合体 I 的结构视角

DOI:
10.1007/978-94-007-4138-6
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发表时间:
2012
期刊:
影响因子:
5.7
通讯作者:
L. Sazanov
L. Sazanov
中科院分区:
医学1区
文献类型:
--
作者:
L. Sazanov

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复合物I是呼吸链的第一个酶,在细胞能量产生中起着核心作用。它与许多人类神经退行性疾病以及衰老有关。它是最大的膜蛋白复合物之一,大小从0.5到1 MDa不等,是由亲水性和膜结构域组成的L形组装体。以前,我们确定了在几个氧化还原状态的亲水性结构域的结构。建立了电子通过7个Fe-S团簇从NADH转移到醌的途径。最近,我们解决了7个膜结构域亚基中的6个的结构,并描述了整个细菌复合物I的结构。酶结构表征的这一进展最终使我们开始理解这台大分子机器的机制。电子转移和质子易位之间的耦合机制涉及长程构象变化,部分由长α-螺旋协调,类似于蒸汽机的耦合杆。
Complex I is the first enzyme of the respiratory chain and plays a central role in cellular energy production. It has been implicated in many human neurodegenerative diseases, as well as in ageing. One of the biggest membrane protein complexes, varying in size from 0.5 to 1 MDa, it is an L-shaped assembly consisting of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain in several redox states. It established the pathway for electron transfer from NADH to quinone via seven Fe-S clusters. Recently, we solved the structure of 6 out of 7 membrane domain subunits and described the architecture the entire bacterial complex I. This progress in structural characterization of the enzyme finally allows us to begin to understand the mechanism of this large molecular machine. The proposed mechanism of coupling between electron transfer and proton translocation involves long-range conformational changes, coordinated in part by a long α-helix, akin to the coupling rod of a steam engine.
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