Structure and functionality of a multimeric human COQ7:COQ9 complex Journal Article uri icon



  • AbstractCoenzyme Q (CoQ, ubiquinone) 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 a structure and functional analyses of a substrate- and NADH-bound oligomeric complex comprised of two complex Q subunits: the hydroxylase COQ7, which performs the penultimate step in CoQ biosynthesis, and the prenyl lipid-binding protein COQ9. We reveal that COQ7 adopts a modified ferritin-like fold with an extended hydrophobic access channel whose substrate binding capacity is enhanced by COQ9. Using molecular dynamics simulations, we further show that two COQ7:COQ9 heterodimers form a curved tetramer that deforms the membrane, potentially opening a pathway for CoQ intermediates to translocate from within the bilayer to the proteins’ lipid-binding sites. Two such tetramers assemble into a soluble octamer, closed like a capsid, with lipids captured within. Together, these observations indicate that COQ7 and COQ9 cooperate to access hydrophobic precursors and coordinate subsequent synthesis steps toward producing mature CoQ.

publication date

  • November 15, 2021

has restriction

  • green

Date in CU Experts

  • January 30, 2022 1:34 AM

Full Author List

  • Manicki M; Aydin H; Abriata LA; Overmyer KA; Guerra RM; Coon JJ; Peraro MD; Frost A; Pagliarini DJ

author count

  • 9

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