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PreprintCited by 14Enzyme Structure and FunctionMitochondrial Function and PathologyATP Synthase and ATPases Research

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

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Ivanov, Bozhidar S., Bridges, Hannah R., Jarman, Owen D., Hirst, Judy·2024·Nature Communications
DOI 10.1101/2024.05.14.594153PMC PMC11522691

Preprint — published as 10.1038/s41467-024-53679-3

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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.

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Metadata

Authors
Ivanov, B. S., Bridges, H. R., Jarman, O. D., & Hirst, J.
Affiliations
University of Cambridge (GB)
Corresponding author
Hirst, Judy
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2024-05-14
Volume
15
Issue
1
Pages
9340-9340
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2024.05.14.594153
PMC
PMC11522691
OpenAlex
W4403868698
Cited by
14
References
1
Citations by year
2026: 6 · 2025: 7 · 2024: 1
FWCI
1.36
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Diamond Light Source
  • Medical Research Council (MC_UU_00015/2, MC_UU_00015/7, COVID-19)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
mitochondrial complex I, Paracoccus denitrificans, nanodiscs, NDUFS4, catalytic mechanism, mitochondrial evolution, Alphaproteobacteria, structure functions
MeSH terms
Bacterial Proteins, Methyltransferases, Models, Molecular, Paracoccus denitrificans, Protein Subunits, Electron Transport Complex I

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