7SSS

Structure of the NADH-bound human COQ7:COQ9 complex by single-particle electron cryo-microscopy

Summary for 7SSS

• Entry DOI: 10.2210/pdb7sss/pdb
• EMDB information: 25413
• Descriptor: Ubiquinone biosynthesis protein COQ9, mitochondrial, 5-demethoxyubiquinone hydroxylase, mitochondrial, (1S)-2-{[(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE, ... (6 entities in total)
• Functional Keywords: hydroxylase, complex, lipid, enzyme, nadh, coenzymeq, isoprene, opp, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 266375.46

Authors

Aydin, H.,Frost, A. (deposition date: 2021-11-11, release date: 2022-11-02, Last modification date: 2024-06-05)

Primary citation

Manicki, M.,Aydin, H.,Abriata, L.A.,Overmyer, K.A.,Guerra, R.M.,Coon, J.J.,Dal Peraro, M.,Frost, A.,Pagliarini, D.J.
Structure and functionality of a multimeric human COQ7:COQ9 complex.
Mol.Cell, 82:4307-4323.e10, 2022

PubMed Abstract: 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.

PubMed: 36306796
DOI: 10.1016/j.molcel.2022.10.003

Experimental method

ELECTRON MICROSCOPY (2.4 Å)