Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):2982-2987. doi: 10.1073/pnas.1800195115. Epub 2018 Mar 7.
Succinate:quinone oxidoreductase (SQR) functions in energy metabolism, coupling the tricarboxylic acid cycle and electron transport chain in bacteria and mitochondria. The biogenesis of flavinylated SdhA, the catalytic subunit of SQR, is assisted by a highly conserved assembly factor termed SdhE in bacteria via an unknown mechanism. By using X-ray crystallography, we have solved the structure of SdhE in complex with SdhA to 2.15-Å resolution. Our structure shows that SdhE makes a direct interaction with the flavin adenine dinucleotide-linked residue His45 in SdhA and maintains the capping domain of SdhA in an "open" conformation. This displaces the catalytic residues of the succinate dehydrogenase active site by as much as 9.0 Å compared with SdhA in the assembled SQR complex. These data suggest that bacterial SdhE proteins, and their mitochondrial homologs, are assembly chaperones that constrain the conformation of SdhA to facilitate efficient flavinylation while regulating succinate dehydrogenase activity for productive biogenesis of SQR.
醌氧化还原酶（SQR）在细菌和线粒体的能量代谢中发挥作用，将三羧酸循环和电子传递链偶联起来。黄素化 SdhA 的生物发生，即 SQR 的催化亚基，由一种高度保守的组装因子 SdhE 通过未知的机制在细菌中辅助。通过使用 X 射线晶体学，我们以 2.15-Å 的分辨率解决了 SdhE 与 SdhA 复合物的结构。我们的结构表明，SdhE 与 SdhA 中连接黄素腺嘌呤二核苷酸的残基 His45 直接相互作用，并保持 SdhA 的盖帽结构域处于“打开”构象。与组装的 SQR 复合物中的 SdhA 相比，这将琥珀酸脱氢酶活性位点的催化残基位移了多达 9.0 Å。这些数据表明，细菌 SdhE 蛋白及其线粒体同源物是组装伴侣，它们限制 SdhA 的构象，以促进黄素化的有效进行，同时调节琥珀酸脱氢酶的活性，以促进 SQR 的有效生物发生。
