Structure of the membrane domain of respiratory complex I
Structure of the membrane domain of respiratory complex I
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DOI：
10.1038/nature10330
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发表时间：
2011-08-25
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.;Sazanov, Leonid A.
复合体I是呼吸链上第一个也是最大的酶，它将NADH和泛醌之间的电子传递偶联到四个质子的跨膜转移。它在细胞能量生产中起着核心作用，并与许多人类神经退行性疾病有关。L形状的酶由亲水结构域和膜结构域组成。在此之前，我们确定了亲水结构域的结构。在这里，我们报道了大肠杆菌复合体I膜结构域在3.0埃分辨率下的晶体结构。它包括NuoL、NuoM、Nuon、NuoA、NuoJ和NuoK六个亚基，有55个跨膜螺旋。同源的反向转运蛋白样亚单位L、M和N的折叠是新的，具有五个跨膜螺旋的两个倒置结构重复序列，异常地面对面排列。每个重复序列包括一个不连续的跨膜螺旋，并形成跨膜通道的一半。一个保守的极性残基网络连接了两个半通道，完成了质子转运途径。出乎意料的是，赖氨酸而不是羧酸残基是这些亚基中质子泵的主要成分。第四个可能的质子转移通道位于N、K、J和A亚基的界面上。结构表明，络合物I中唯一的质子转移涉及六个对称结构元素的协调构象变化。
Complex I is the first and largest enzyme of the respiratory chain, coupling electron transfer between NADH and ubiquinone to the translocation of four protons across the membrane. It has a central role in cellular energy production and has been implicated in many human neurodegenerative diseases. The L-shaped enzyme consists of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 angstrom resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-like subunits L, M and N is novel, with two inverted structural repeats of five transmembrane helices arranged, unusually, face-to-back. Each repeat includes a discontinuous transmembrane helix and forms half of a channel across the membrane. A network of conserved polar residues connects the two half-channels, completing the proton translocation pathway. Unexpectedly, lysines rather than carboxylate residues act as the main elements of the proton pump in these subunits. The fourth probable proton-translocation channel is at the interface of subunits N, K, J and A. The structure indicates that proton translocation in complex I, uniquely, involves coordinated conformational changes in six symmetrical structural elements.