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Publication Abstract from PubMed

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.

Structure and functionality of a multimeric human COQ7:COQ9 complex.,Manicki M, Aydin H, Abriata LA, Overmyer KA, Guerra RM, Coon JJ, Dal Peraro M, Frost A, Pagliarini DJ Mol Cell. 2022 Nov 17;82(22):4307-4323.e10. doi: 10.1016/j.molcel.2022.10.003. , Epub 2022 Oct 27. PMID:36306796^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.