Functional Modules and Structural Basis of Conformational Coupling in Mitochondrial Complex I
Functional Modules and Structural Basis of Conformational Coupling in Mitochondrial Complex I
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DOI：
10.1126/science.1191046
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发表时间：
2010-07-23
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：
Hunte, Carola;Zickermann, Volker;Brandt, Ulrich
质子泵呼吸复合物I是最大和最复杂的膜蛋白复合物之一。它的功能对于有氧细胞的有效能量供应至关重要，并且在许多神经退行性疾病中涉及功能障碍。在这里，我们报告了线粒体复合物I的X射线晶体学分析。所有的铁-硫簇相对于膜臂的位置被确定在完整的酶复合物。泛醌还原位点位于膜结构域上方接近30埃处。功能模块的安排表明构象耦合的氧化还原化学与质子泵，基本上排除了直接的机制。我们建议，一个类似的60埃长的螺旋传输元件是至关重要的转换构象能量的质子泵元件在膜臂的远端模块。
Proton-pumping respiratory complex I is one of the largest and most complicated membrane protein complexes. Its function is critical for efficient energy supply in aerobic cells, and malfunctions are implicated in many neurodegenerative disorders. Here, we report an x-ray crystallographic analysis of mitochondrial complex I. The positions of all iron-sulfur clusters relative to the membrane arm were determined in the complete enzyme complex. The ubiquinone reduction site resides close to 30 angstroms above the membrane domain. The arrangement of functional modules suggests conformational coupling of redox chemistry with proton pumping and essentially excludes direct mechanisms. We suggest that a similar to 60-angstrom-long helical transmission element is critical for transducing conformational energy to proton-pumping elements in the distal module of the membrane arm.