The architecture of respiratory complex I
The architecture of respiratory complex I
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DOI：
10.1038/nature09066
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发表时间：
2010-05-27
期刊：
影响因子：
64.8
通讯作者：
Sazanov, Leonid A.
中科院分区：
文献类型：
--
作者：
Efremov, Rouslan G.;Baradaran, Rozbeh;Sazanov, Leonid A.
复合体I是呼吸链的第一个酶，在细胞能量产生中起核心作用，通过未知的机制将NADH和苯二酚之间的电子转移耦合到质子转移。复合体I功能障碍与许多人类神经退行性疾病有关。我们已经确定了它的亲水结构域的结构。在这里，我们报告了来自大肠杆菌的复合体I的膜结构域在3.9埃分辨率下的α-螺旋结构。反转运蛋白样亚单位NuoL/M/N各含有14个保守的跨膜(TM)螺旋。其中两个是不连续的，就像在一些运输机中一样。出乎意料的是，NuoL亚基还含有一个110埃长的两亲性α-螺旋，几乎覆盖了整个结构域的长度。此外，我们还以4.5埃的分辨率确定了嗜热热菌的整个络合物I的结构。L形状的组件由膜结构域的α螺旋模型和已知的亲水结构域组成，膜结构域有63个TM螺旋。该复合体的结构为耦合机制提供了强有力的线索：两个主要结构域界面上的构象变化可能会驱动NuoL的两亲性长α螺旋做活塞式运动，倾斜附近不连续的TM螺旋，导致质子转移。
Complex I is the first enzyme of the respiratory chain and has a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation by an unknown mechanism. Dysfunction of complex I has been implicated in many human neurodegenerative diseases. We have determined the structure of its hydrophilic domain previously. Here, we report the alpha-helical structure of the membrane domain of complex I from Escherichia coli at 3.9 angstrom resolution. The antiporter-like subunits NuoL/M/N each contain 14 conserved transmembrane (TM) helices. Two of them are discontinuous, as in some transporters. Unexpectedly, subunit NuoL also contains a 110-angstrom long amphipathic alpha-helix, spanning almost the entire length of the domain. Furthermore, we have determined the structure of the entire complex I from Thermus thermophilus at 4.5 angstrom resolution. The L-shaped assembly consists of the alpha-helical model for the membrane domain, with 63 TM helices, and the known structure of the hydrophilic domain. The architecture of the complex provides strong clues about the coupling mechanism: the conformational changes at the interface of the two main domains may drive the long amphipathic alpha-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation.