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 Escherichia coli 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.

琥珀酸：醌氧化还原酶（SQR）在能量代谢中起作用，将三羧酸循环与细菌和线粒体中的电子传输链耦合。黄藻酰化SdhA（SQR的催化亚基）的生物发生是通过未知机制在细菌中被高度保守的称为SdhE的装配因子辅助的。通过使用X射线晶体学，我们已经解决了大肠杆菌的结构具有SdhA至2.15Å分辨率的SdhE。我们的结构表明，SdhE与SdhA中的黄素腺嘌呤二核苷酸连接的残基His45直接相互作用，并使SdhA的封端结构域保持“开放”构象。与组装的SQR络合物中的SdhA相比，琥珀酸脱氢酶活性位点的催化残基移位了9.0Å。这些数据表明细菌SdhE蛋白及其线粒体同源物是装配伴侣，它们约束SdhA的构象，以促进有效的黄素化，同时调节琥珀酸脱氢酶的活性，从而促进SQR的生物发生。