Architecture of mammalian respiratory complex I.
Architecture of mammalian respiratory complex I.
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DOI：
10.1038/nature13686
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发表时间：
2014-11-06
期刊：
影响因子：
64.8
通讯作者：
Hirst, Judy
中科院分区：
文献类型：
--
作者：
Vinothkumar, Kutti R.;Zhu, Jiapeng;Hirst, Judy
复合体I(NADH：泛醌氧化还原酶)是哺乳动物线粒体氧化磷酸化所必需的。它结合了从NADH到泛醌的电子转移和跨能量转导内膜的质子转移，为呼吸提供电子并驱动ATP合成。哺乳动物复合体I包含44个不同的核和线粒体编码亚基，总质量为1个丙二醛。14个保守的‘核心’亚基在结构上定义在最小的细菌复合体中，但30个‘额外’亚基的结构和排列尚不清楚。在这里，我们描述了由单粒子电子冷冻显微镜确定的来自牛心脏线粒体的5？分辨率结构，该线粒体是人类酶的近亲。我们给出了哺乳动物核心亚基的结构，包括8个铁硫簇和60个跨膜螺旋，识别了18个额外的跨膜螺旋，并对14个额外的亚基进行了分配和建模。因此，我们大大提高了对哺乳动物复合体I的结构及其核心结构域周围的额外系综结构的了解。我们的结构提供了对多余亚基在调节、组装和动态平衡中的作用的洞察，并为理解导致各种人类疾病的突变的影响提供了基础。
Complex I (NADH:ubiquinone oxidoreductase) is essential for oxidative phosphorylation in mammalian mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the energy-transducing inner membrane, providing electrons for respiration and driving ATP synthesis. Mammalian complex I contains 44 different nuclear- and mitochondrial-encoded subunits, with a combined mass of 1 MDa. The fourteen conserved ‘core’ subunits have been structurally defined in the minimal, bacterial complex, but the structures and arrangement of the 30 ‘supernumerary’ subunits are unknown. Here, we describe a 5 Å resolution structure of complex I from Bos taurus heart mitochondria, a close relative of the human enzyme, determined by single-particle electron cryo-microscopy. We present the structures of the mammalian core subunits that contain eight iron-sulphur clusters and 60 transmembrane helices, identify 18 supernumerary transmembrane helices, and assign and model 14 supernumerary subunits. Thus, we significantly advance knowledge of the structure of mammalian complex I and the architecture of its supernumerary ensemble around the core domains. Our structure provides insights into the roles of the supernumerary subunits in regulation, assembly and homeostasis, and a basis for understanding the effects of mutations that cause a diverse range of human diseases.
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影响因子：
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作者：
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影响因子：
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