Atomic structure of the entire mammalian mitochondrial complex I.
Atomic structure of the entire mammalian mitochondrial complex I.
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DOI：
10.1038/nature19794
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发表时间：
2016-10-20
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：
Fiedorczuk, Karol;Letts, James A.;Degliesposti, Gianluca;Kaszuba, Karol;Skehel, Mark;Sazanov, Leonid A.
线粒体复合物I通过将电子从NADH转移到泛醌并结合质子跨膜转运在细胞能量产生中起关键作用。它是呼吸链中最大的蛋白质组装体，总质量为970 kDa。在这里，我们提出了一个几乎完整的原子结构的绵羊线粒体复合物I在3.9 μ m分辨率，解决了冷冻电子显微镜辅助交联/质谱映射。所有14个保守的核心和31个特异性的额外亚基在L形分子内被解析。亲水性基质臂含有FMN和8个参与电子转移的铁硫簇，膜臂含有78个跨膜螺旋，主要由参与质子转运的反转运蛋白样亚基贡献。多余的亚基在保守的核心周围形成一个相互连接的稳定外壳。紧密结合的脂质（包括心磷脂）进一步稳定疏水亚基之间的相互作用。具有可能的调节作用的亚基含有额外的辅因子，NADPH和两个磷酸泛酰巯基乙胺分子，被揭示参与亚基间的相互作用。我们观察到两种不同的构象的复合物，这可能与构象驱动的耦合机制和酶的活性/失活过渡。我们的结构提供了深入了解复杂I机制，组装，成熟和功能障碍，允许致病突变的详细分子分析。
Mitochondrial complex I plays a key role in cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane. It is the largest protein assembly of the respiratory chain with total mass of 970 kDa. Here we present a nearly complete atomic structure of ovine mitochondrial complex I at 3.9 Å resolution, solved by cryo-electron microscopy aided by crosslinking/mass-spectrometry mapping. All 14 conserved core and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm harbours FMN and 8 iron-sulphur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, revealed to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active/deactive transition of the enzyme. Our structure provides insight into complex I mechanism, assembly, maturation and dysfunction, allowing detailed molecular analysis of disease-causing mutations.
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影响因子：
2.9
作者：
Krivov, Georgii G.;Shapovalov, Maxim V.;Dunbrack, Roland L., Jr.
通讯作者：
Dunbrack, Roland L., Jr.
电子计数和束诱导运动校正可实现近原子分辨率的单粒子冷冻电镜。
影响因子：
48
作者：
Li, Xueming;Mooney, Paul;Zheng, Shawn;Booth, Christopher R.;Braunfeld, Michael B.;Gubbens, Sander;Agard, David A.;Cheng, Yifan
通讯作者：
Cheng, Yifan
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
7
作者：
Carroll, J;Fearnley, IM;Walker, JE
通讯作者：
Walker, JE