Structure and functionality of a multimeric human COQ7:COQ9 complex.

Mateusz Manicki, Halil Aydin, Luciano A Abriata, Katherine A Overmyer, Rachel M Guerra, Joshua J Coon, Matteo Dal Peraro, Adam Frost, David J Pagliarini

Molecular cell 2022 Nov 17

filter terms:

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 cooperate to access hydrophobic precursors within the membrane and coordinate subsequent synthesis steps toward producing CoQ. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Mateusz Manicki, Halil Aydin, Luciano A Abriata, Katherine A Overmyer, Rachel M Guerra, Joshua J Coon, Matteo Dal Peraro, Adam Frost, David J Pagliarini. Structure and functionality of a multimeric human COQ7:COQ9 complex. Molecular cell. 2022 Nov 17;82(22):4307-4323.e10