Structure and functionality of a multimeric human COQ7:COQ9 complex

Coenzyme Q (CoQ) is a redox-active lipid essential for core metabolic pathways and antioxidant defense. CoQ is synthesized upon the mitochondrial inner membrane by an ill-defined complex Q metabolon. Here, we present structure-function analyses of a lipid-, substrate-, and NADH-bound complex comprising two complex Q subunits: the hydroxylase COQ7 and the lipid-binding protein COQ9. We reveal that COQ7 adopts a ferritin-like fold with a hydrophobic channel whose substrate-binding capacity is enhanced by COQ9. Using molecular dynamics, we further show that two COQ7:COQ9 heterodimers form a curved tetramer that deforms the membrane, potentially opening a pathway for the CoQ intermediates to translocate from the bilayer to the proteins' lipid-binding sites. Two such tetramers assemble into a soluble octamer with a pseudo-bilayer of lipids captured within. Together, these observations indicate that COQ7 and COQ9 coop-erate to access hydrophobic precursors within the membrane and coordinate subsequent synthesis steps toward producing CoQ.

Automated summary

This study presents structure-function analyses of a complex comprising COQ7 and COQ9, revealing their roles in the synthesis of CoQ. The findings suggest that COQ7 and COQ9 interact to form a complex that facilitates the translocation of CoQ intermediates from the membrane to the protein's lipid-binding sites.