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dc.creatorMoreno Beltrán, José Blases
dc.creatorGuerra Castellano, Alejandraes
dc.creatorDíaz Quintana, Antonio Jesúses
dc.creatorConte, Rebecca deles
dc.creatorGarcía Mauriño, Sofía M.es
dc.creatorGonzález Arzola, Katiuskaes
dc.creatorRosa Acosta, Miguel Ángel de laes
dc.creatorDíaz Moreno, Irenees
dc.date.accessioned2018-01-02T15:12:49Z
dc.date.available2018-01-02T15:12:49Z
dc.date.issued2017
dc.identifier.citationMoreno Beltrán, J.B., Guerra Castellano, A., Díaz Quintana, A., Conte, R.d., García Mauriño, S.M., González Arzola, K.,...,Díaz Moreno, I. (2017). Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48. Proceedings of the National Academy of Sciences, 114 (15), E3041-E3050.
dc.identifier.issn0027-8424es
dc.identifier.urihttp://hdl.handle.net/11441/68113
dc.description.abstractRegulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation—in particular, at tyrosine 48—is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methylL-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects.es
dc.description.sponsorshipEspaña, MINECO BFU2015-71017-P/BMC and BFU2015- 19451/BMCes
dc.description.sponsorshipUnión Europea, Bio-NMR-00130 and CALIPSO-312284es
dc.description.sponsorshipEspaña, Ministerio de Educación AP2009-4092es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherNational Academy of Scienceses
dc.relation.ispartofProceedings of the National Academy of Sciences, 114 (15), E3041-E3050.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectcytochrome ces
dc.subjectmitochondrial dysfunctiones
dc.subjectnuclear magnetic resonancees
dc.subjectphosphorylationes
dc.subjectrespiratory supercomplexeses
dc.titleStructural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48es
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessrightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Moleculares
dc.relation.projectIDBFU2015-71017-P/BMCes
dc.relation.projectIDBFU2015- 19451/BMCes
dc.relation.projectIDBio-NMR-00130es
dc.relation.projectIDCALIPSO-312284es
dc.relation.projectIDAP2009-4092es
dc.relation.publisherversionhttp://www.pnas.org/content/114/15/E3041.full.pdfes
dc.identifier.doi10.1073/pnas.1618008114es
idus.format.extent9 p.es
dc.journaltitleProceedings of the National Academy of Scienceses
dc.publication.volumen114es
dc.publication.issue15es
dc.publication.initialPageE3041es
dc.publication.endPageE3050es
dc.contributor.funderMinisterio de Economía y Competitividad (MINECO). España
dc.contributor.funderEuropean Union (UE)

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