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-Structure paper
タイトル | Structure and functionality of a multimeric human COQ7:COQ9 complex. |
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ジャーナル・号・ページ | Mol Cell, Vol. 82, Issue 22, Page 4307-4323.e10, Year 2022 |
掲載日 | 2022年11月17日 |
著者 | Mateusz Manicki / Halil Aydin / Luciano A Abriata / Katherine A Overmyer / Rachel M Guerra / Joshua J Coon / Matteo Dal Peraro / Adam Frost / David J Pagliarini / |
PubMed 要旨 | 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" ...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. |
リンク | Mol Cell / PubMed:36306796 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.4 - 3.5 Å |
構造データ | EMDB-25412, PDB-7ssp: EMDB-25413, PDB-7sss: |
化合物 | ChemComp-PEV: ChemComp-8PP: ChemComp-NAD: ChemComp-HOH: |
由来 |
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キーワード | MEMBRANE PROTEIN / hydroxylase / complex / lipid / enzyme / NADH / coenzymeQ / isoprene / OPP |