RT Journal Article
SR Electronic
T1 Structure and functionality of a multimeric human COQ7:COQ9 complex
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.15.468694
DO 10.1101/2021.11.15.468694
A1 Mateusz Manicki
A1 Halil Aydin
A1 Luciano A. Abriata
A1 Katherine A. Overmyer
A1 Rachel M. Guerra
A1 Joshua J. Coon
A1 Matteo Dal Peraro
A1 Adam Frost
A1 David J. Pagliarini
YR 2021
UL http://biorxiv.org/content/early/2021/11/15/2021.11.15.468694.abstract
AB Coenzyme 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.Competing Interest StatementJoshua J. Coon is a consultant for Thermo Scientific. Adam Frost is a shareholder and consultant for Relay Therapeutics, LLC.