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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
29 Oct 2024
Historique:
received: 19 08 2024
accepted: 21 10 2024
medline: 30 10 2024
pubmed: 30 10 2024
entrez: 30 10 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 39472559
doi: 10.1038/s41467-024-53679-3
pii: 10.1038/s41467-024-53679-3
doi:

Substances chimiques

Electron Transport Complex I EC 7.1.1.2
Bacterial Proteins 0
Protein Subunits 0
Methyltransferases EC 2.1.1.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

9340

Subventions

Organisme : RCUK | Medical Research Council (MRC)
ID : MC_UU_00015/2
Organisme : RCUK | Medical Research Council (MRC)
ID : MC_UU_00015/2
Organisme : RCUK | Medical Research Council (MRC)
ID : MC_UU_00015/2
Organisme : RCUK | Medical Research Council (MRC)
ID : MC_UU_00015/2

Informations de copyright

© 2024. The Author(s).

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Auteurs

Bozhidar S Ivanov (BS)

The Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Keith Peters Building, Cambridge Biomedical Campus, Cambridge, UK.

Hannah R Bridges (HR)

The Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Keith Peters Building, Cambridge Biomedical Campus, Cambridge, UK.
Structura Biotechnology Inc., Toronto, Canada.

Owen D Jarman (OD)

The Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Keith Peters Building, Cambridge Biomedical Campus, Cambridge, UK.
Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.

Judy Hirst (J)

The Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Keith Peters Building, Cambridge Biomedical Campus, Cambridge, UK. jh480@cam.ac.uk.

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