dc.creator | Moreno Beltrán, José Blas | es |
dc.creator | Guerra Castellano, Alejandra | es |
dc.creator | Díaz Quintana, Antonio Jesús | es |
dc.creator | Conte, Rebecca del | es |
dc.creator | García Mauriño, Sofía M. | es |
dc.creator | González Arzola, Katiuska | es |
dc.creator | Rosa Acosta, Miguel Ángel de la | es |
dc.creator | Díaz Moreno, Irene | es |
dc.date.accessioned | 2018-01-02T15:12:49Z | |
dc.date.available | 2018-01-02T15:12:49Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Moreno 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.issn | 0027-8424 | es |
dc.identifier.uri | http://hdl.handle.net/11441/68113 | |
dc.description.abstract | Regulation 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.sponsorship | España, MINECO BFU2015-71017-P/BMC and BFU2015- 19451/BMC | es |
dc.description.sponsorship | Unión Europea, Bio-NMR-00130 and CALIPSO-312284 | es |
dc.description.sponsorship | España, Ministerio de Educación AP2009-4092 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | National Academy of Sciences | es |
dc.relation.ispartof | Proceedings of the National Academy of Sciences, 114 (15), E3041-E3050. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | cytochrome c | es |
dc.subject | mitochondrial dysfunction | es |
dc.subject | nuclear magnetic resonance | es |
dc.subject | phosphorylation | es |
dc.subject | respiratory supercomplexes | es |
dc.title | Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48 | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular | es |
dc.relation.projectID | BFU2015-71017-P/BMC | es |
dc.relation.projectID | BFU2015- 19451/BMC | es |
dc.relation.projectID | Bio-NMR-00130 | es |
dc.relation.projectID | CALIPSO-312284 | es |
dc.relation.projectID | AP2009-4092 | es |
dc.relation.publisherversion | http://www.pnas.org/content/114/15/E3041.full.pdf | es |
dc.identifier.doi | 10.1073/pnas.1618008114 | es |
idus.format.extent | 9 p. | es |
dc.journaltitle | Proceedings of the National Academy of Sciences | es |
dc.publication.volumen | 114 | es |
dc.publication.issue | 15 | es |
dc.publication.initialPage | E3041 | es |
dc.publication.endPage | E3050 | es |
dc.contributor.funder | Ministerio de Economía y Competitividad (MINECO). España | |
dc.contributor.funder | European Union (UE) | |