The roles of SDHAF2 and dicarboxylate in covalent flavinylation of SDHA, the human complex II flavoprotein
Pankaj Sharma, Elena Maklashina, Gary Cecchini, T.M. Iverson
Abstract
Significance Complex II is a membrane-spanning machine that supports respiration in all kingdoms. Complex II insufficiency can result from mutations in any of the genes encoding its subunits or from incorrect assembly. Here, we evaluate how a small molecule dicarboxylate works in synergy with the SDHAF2 assembly factor to promote covalent attachment of FAD to the SDHA subunit. We determine the structure of the human SDHA-SDHAF2 assembly intermediate with the dicarboxylate oxaloacetate and reveal how this pose contributes to complex II maturation. Our findings provide the structure of a part of human complex II and identify how SDHAF2 and the dicarboxylate organize the active site. Comparison to previous work reveals that multiple catalytic states change the active site parameters.