Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, United States.
Molecular Biology Division, San Francisco VA Health Care System, San Francisco, CA 94121, United States; Department of Biochemistry & Biophysics, University of California, San Francisco, CA 94158, United States.
Curr Opin Struct Biol. 2019 Dec;59:38-46. doi: 10.1016/j.sbi.2019.01.027. Epub 2019 Mar 7.
Respiratory complexes are complicated multi-subunit cofactor-containing machines that allow cells to harvest energy from the environment. Maturation of these complexes requires protein folding, cofactor insertion, and assembly of multiple subunits into a final, functional complex. Because the intermediate states in complex maturation are transitory, these processes are poorly understood. This review gives an overview of the process of maturation in respiratory complex II with a focus on recent structural studies on intermediates formed during covalent flavinylation of the catalytic subunit, SDHA. Covalent flavinylation has an evolutionary significance because variants of complex II enzymes with the covalent ligand removed by mutagenesis cannot oxidize succinate, but can still perform the reverse reaction and reduce fumarate. Since succinate oxidation is a key step of aerobic respiration, the covalent bond of complex II appears to be important for aerobic life.
呼吸复合物是复杂的多亚基辅酶包含机器,使细胞能够从环境中获取能量。这些复合物的成熟需要蛋白质折叠、辅酶插入以及多个亚基组装成最终的功能性复合物。由于复合物成熟的中间状态是短暂的,这些过程还不太清楚。这篇综述概述了呼吸复合物 II 的成熟过程,重点介绍了最近在催化亚基 SDHA 的共价黄素化过程中形成的中间结构的研究。共价黄素化具有进化意义,因为通过突变去除共价配体的复合物 II 酶变体不能氧化琥珀酸,但仍可以进行相反的反应并还原延胡索酸。由于琥珀酸氧化是有氧呼吸的关键步骤,因此复合物 II 的共价键似乎对有氧生命很重要。