Mechanistic insight from the crystal structure of mitochondrial complex I
Mechanistic insight from the crystal structure of mitochondrial complex I
复制标题
DOI：
10.1126/science.1259859
复制
发表时间：
2015-01-02
期刊：
影响因子：
56.9
通讯作者：
Brandt, Ulrich
中科院分区：
文献类型：
--
作者：
Zickermann, Volker;Wirth, Christophe;Brandt, Ulrich
线粒体呼吸链的质子泵复合体I是最大、最复杂的膜蛋白复合体之一。该酶对真核细胞中的氧化能量转换有很大贡献。它的故障与许多遗传性和退行性疾病有关。我们报道了线粒体复合体I的X射线结构，分辨率为3.6到3.9埃，详细描述了执行生物能量功能的中央亚基。一条连续的碱性残基和酸性残基的轴心穿过膜臂，将亲水臂中的泛醌还原位置连接到四个假定的质子泵单元。底物类似物抑制剂的结合位置和预测的泛醌结合位置的阻断为酶的“失活”形式提供了一个模型。拟议的向活性形式的转变是基于泛醌还原中心的协调结构重排，为质子泵浦的两态稳定-变化机制提供了支持。
Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complicated membrane protein complexes. The enzyme contributes substantially to oxidative energy conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. We report the x-ray structure of mitochondrial complex I at a resolution of 3.6 to 3.9 angstroms, describing in detail the central subunits that execute the bioenergetic function. A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the "deactive" form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site, providing support for a two-state stabilization-change mechanism of proton pumping.