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dc.contributor.authorAgip, Ahmed-Noor Aen
dc.contributor.authorBlaza, James Nen
dc.contributor.authorBridges, Hannahen
dc.contributor.authorViscomi, Carloen
dc.contributor.authorRawson, Shaunen
dc.contributor.authorMuench, Stephen Pen
dc.contributor.authorHirst, Judyen
dc.date.accessioned2018-08-15T15:22:45Z
dc.date.available2018-08-15T15:22:45Z
dc.date.issued2018-07en
dc.identifier.issn1545-9993
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/278849
dc.description.abstractComplex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recently, cryoEM analyses have produced close-to-complete models of all 45 subunits in the bovine, ovine and porcine complexes, and identifed two states relevant to complex I in ischemia-reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically-relevant model system, in the ‘active’ state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside-kinase homolog, and define mechanistically-critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the ‘deactive’ state and with known bacterial structures we identify differences in helical geometry in the membrane domain that occur upon activation, or that alter the positions of catalytically-important charged residues. Our results demonstrate the capability of cryoEM analyses to challenge and develop mechanistic models for mammalian complex I.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSpringer Nature
dc.subjectMitochondria, Hearten
dc.subjectAnimalsen
dc.subjectMiceen
dc.subjectUbiquinoneen
dc.subjectElectron Transport Complex Ien
dc.subjectNADH Dehydrogenaseen
dc.subjectNucleotidesen
dc.subjectPhospholipidsen
dc.subjectProtein Subunitsen
dc.subjectCryoelectron Microscopyen
dc.subjectBinding Sitesen
dc.subjectEnzyme Activationen
dc.subjectProtein Structure, Quaternaryen
dc.subjectModels, Molecularen
dc.subjectProtein Structural Elementsen
dc.titleCryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states.en
dc.typeArticle
prism.endingPage556
prism.issueIdentifier7en
prism.publicationDate2018en
prism.publicationNameNature structural & molecular biologyen
prism.startingPage548
prism.volume25en
dc.identifier.doi10.17863/CAM.26226
dcterms.dateAccepted2018-04-26en
rioxxterms.versionofrecord10.1038/s41594-018-0073-1en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-07en
dc.contributor.orcidBlaza, James N [0000-0001-5420-2116]
dc.contributor.orcidBridges, Hannah [0000-0001-6890-6050]
dc.contributor.orcidViscomi, Carlo [0000-0001-6050-0566]
dc.contributor.orcidRawson, Shaun [0000-0002-2973-2630]
dc.contributor.orcidMuench, Stephen P [0000-0001-6869-4414]
dc.contributor.orcidHirst, Judy [0000-0001-8667-6797]
dc.identifier.eissn1545-9985
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_U105663141)
pubs.funder-project-idMRC (MC_UP_1002/1)
pubs.funder-project-idMRC (MC_UP_1002/1)
pubs.funder-project-idMRC (MC_UP_1002/1)
pubs.funder-project-idMRC (MC_UU_00015/8)
rioxxterms.freetoread.startdate2018-12-18


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