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Structure of the turnover-ready state of an ancestral respiratory complex I

Author

Listed:
  • Bozhidar S. Ivanov

    (Cambridge Biomedical Campus)

  • Hannah R. Bridges

    (Cambridge Biomedical Campus
    Structura Biotechnology Inc.)

  • Owen D. Jarman

    (Cambridge Biomedical Campus
    Max Planck Institute for Terrestrial Microbiology)

  • Judy Hirst

    (Cambridge Biomedical Campus)

Abstract

Respiratory complex I is pivotal for cellular energy conversion, harnessing energy from NADH:ubiquinone oxidoreduction to drive protons across energy-transducing membranes for ATP synthesis. Despite detailed structural information on complex I, its mechanism of catalysis remains elusive due to lack of accompanying functional data for comprehensive structure-function analyses. Here, we present the 2.3-Å resolution structure of complex I from the α-proteobacterium Paracoccus denitrificans, a close relative of the mitochondrial progenitor, in phospholipid-bilayer nanodiscs. Three eukaryotic-type supernumerary subunits (NDUFS4, NDUFS6 and NDUFA12) plus a novel L-isoaspartyl-O-methyltransferase are bound to the core complex. Importantly, the enzyme is in a single, homogeneous resting state that matches the closed, turnover-ready (active) state of mammalian complex I. Our structure reveals the elements that stabilise the closed state and completes P. denitrificans complex I as a unified platform for combining structure, function and genetics in mechanistic studies.

Suggested Citation

  • Bozhidar S. Ivanov & Hannah R. Bridges & Owen D. Jarman & Judy Hirst, 2024. "Structure of the turnover-ready state of an ancestral respiratory complex I," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53679-3
    DOI: 10.1038/s41467-024-53679-3
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    References listed on IDEAS

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