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-Structure paper
Title | Structure of inhibitor-bound mammalian complex I. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 5261, Year 2020 |
Publish date | Oct 16, 2020 |
Authors | 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 Abstract | 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. |
External links | Nat Commun / PubMed:33067417 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.0 - 3.1 Å |
Structure data | 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) |
Chemicals | ChemComp-SF4: ChemComp-PC1: ChemComp-FES: ChemComp-FMN: ChemComp-3PE: ChemComp-CDL: ChemComp-ATP: ChemComp-NDP: ChemComp-ZN: ChemComp-EHZ: ChemComp-HQH: |
Source |
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Keywords | OXIDOREDUCTASE / NADH / ubiquinone / complex I |