7SSP

Structure of the human COQ7:COQ9 complex by single-particle electron cryo-microscopy, unliganded state

7SSP の概要

• エントリーDOI: 10.2210/pdb7ssp/pdb
• EMDBエントリー: 25412
• 分子名称: Ubiquinone biosynthesis protein COQ9, mitochondrial, 5-demethoxyubiquinone hydroxylase, mitochondrial (2 entities in total)
• 機能のキーワード: hydroxylase, complex, lipid, enzyme, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 239452.04

構造登録者

Aydin, H.,Frost, A. (登録日: 2021-11-11, 公開日: 2022-11-02, 最終更新日: 2025-05-28)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.5 Å)