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-Structure paper
Title | Essential role of accessory subunit LYRM6 in the mechanism of mitochondrial complex I. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 6008, Year 2020 |
Publish date | Nov 26, 2020 |
Authors | Etienne Galemou Yoga / Kristian Parey / Amina Djurabekova / Outi Haapanen / Karin Siegmund / Klaus Zwicker / Vivek Sharma / Volker Zickermann / Heike Angerer / |
PubMed Abstract | Respiratory complex I catalyzes electron transfer from NADH to ubiquinone (Q) coupled to vectorial proton translocation across the inner mitochondrial membrane. Despite recent progress in structure ...Respiratory complex I catalyzes electron transfer from NADH to ubiquinone (Q) coupled to vectorial proton translocation across the inner mitochondrial membrane. Despite recent progress in structure determination of this very large membrane protein complex, the coupling mechanism is a matter of ongoing debate and the function of accessory subunits surrounding the canonical core subunits is essentially unknown. Concerted rearrangements within a cluster of conserved loops of central subunits NDUFS2 (β1-β2 loop), ND1 (TMH5-6 loop) and ND3 (TMH1-2 loop) were suggested to be critical for its proton pumping mechanism. Here, we show that stabilization of the TMH1-2 loop by accessory subunit LYRM6 (NDUFA6) is pivotal for energy conversion by mitochondrial complex I. We determined the high-resolution structure of inactive mutant F89A of eukaryotic complex I from the yeast Yarrowia lipolytica and found long-range structural changes affecting the entire loop cluster. In atomistic molecular dynamics simulations of the mutant, we observed conformational transitions in the loop cluster that disrupted a putative pathway for delivery of substrate protons required in Q redox chemistry. Our results elucidate in detail the essential role of accessory subunit LYRM6 for the function of eukaryotic complex I and offer clues on its redox-linked proton pumping mechanism. |
External links | Nat Commun / PubMed:33243981 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.96 Å |
Structure data | EMDB-10711, PDB-6y79: |
Chemicals | ChemComp-SF4: ChemComp-FES: ChemComp-FMN: ChemComp-NDP: ChemComp-3PE: ChemComp-LMN: ChemComp-ZN: ChemComp-ZMP: ChemComp-PLC: ChemComp-CDL: ChemComp-UQ9: ChemComp-T7X: ChemComp-PSC: |
Source |
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Keywords | OXIDOREDUCTASE / Complex I / NADH dehydrogenase / Mitochondrion proton pumping / Ubiquinone |