Structural study reveals how SDHAF2 and oxaloacetate coordinate to drive SDHA flavinylation in human complex II, highlighting key molecular steps in mitochondrial respiratory chain assembly.
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.
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Sharma et al. (2020) studied this question.
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