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-Structure paper
タイトル | Structure of inhibitor-bound mammalian complex I. |
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ジャーナル・号・ページ | Nat Commun, Vol. 11, Issue 1, Page 5261, Year 2020 |
掲載日 | 2020年10月16日 |
著者 | Hannah R Bridges / Justin G Fedor / James N Blaza / Andrea Di Luca / Alexander Jussupow / Owen D Jarman / John J Wright / Ahmed-Noor A Agip / Ana P Gamiz-Hernandez / Maxie M Roessler / Ville R I Kaila / Judy Hirst / |
PubMed 要旨 | Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power ...Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-Å resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I. |
リンク | Nat Commun / PubMed:33067417 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.0 - 3.1 Å |
構造データ | EMDB-11377, PDB-6zr2: EMDB-11424, PDB-6ztq: EMDB-11425: Cryo-EM structure of respiratory complex I from Mus musculus inhibited by piericidin A at 3.0 A (Falcon 3) |
化合物 | ChemComp-SF4: ChemComp-PC1: ChemComp-FES: ChemComp-FMN: ChemComp-3PE: ChemComp-CDL: ChemComp-ATP: ChemComp-NDP: ChemComp-ZN: ChemComp-EHZ: ChemComp-HQH: |
由来 |
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キーワード | OXIDOREDUCTASE / NADH / ubiquinone / complex I |