000069672 001__ 69672
000069672 005__ 20210618112019.0
000069672 0247_ $$2doi$$a10.1073/pnas.1618008114
000069672 0248_ $$2sideral$$a104669
000069672 037__ $$aART-2017-104669
000069672 041__ $$aeng
000069672 100__ $$aMoreno-Beltrán, B.
000069672 245__ $$aStructural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48
000069672 260__ $$c2017
000069672 5060_ $$aAccess copy available to the general public$$fUnrestricted
000069672 5203_ $$aRegulation 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-methyl-L-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.
000069672 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BFU2015-71017-P-BMC$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2015-19451-BMC$$9info:eu-repo/grantAgreement/EC/FP7/312284/EU/Coordinated Access to Lightsources to Promote Standards and Optimization/CALIPSO$$9info:eu-repo/grantAgreement/EC/FP7/261863/EU/NMR for Structural Biology/BIO-NMR
000069672 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000069672 590__ $$a9.504$$b2017
000069672 591__ $$aMULTIDISCIPLINARY SCIENCES$$b5 / 64 = 0.078$$c2017$$dQ1$$eT1
000069672 592__ $$a6.092$$b2017
000069672 593__ $$aMultidisciplinary$$c2017$$dQ1
000069672 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000069672 700__ $$aGuerra-Castellano, A.
000069672 700__ $$aDíaz-Quintana, A.
000069672 700__ $$aConte, R.D.
000069672 700__ $$aGarcía-Mauriño, S.M.
000069672 700__ $$aDíaz-Moreno, S.
000069672 700__ $$aGonzález-Arzola, K.
000069672 700__ $$aSantos-Ocaña, C.
000069672 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000069672 700__ $$aDe la Rosa, M.A.
000069672 700__ $$aTurano, P.
000069672 700__ $$aDíaz-Moreno, I.
000069672 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000069672 773__ $$g114, 15 (2017), E3041-E3050$$pProc. Natl. Acad. Sci.$$tProceedings of the National Academy of Sciences$$x0027-8424
000069672 8564_ $$s2064263$$uhttps://zaguan.unizar.es/record/69672/files/texto_completo.pdf$$yVersión publicada
000069672 8564_ $$s139862$$uhttps://zaguan.unizar.es/record/69672/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000069672 909CO $$ooai:zaguan.unizar.es:69672$$particulos$$pdriver
000069672 951__ $$a2021-06-18-11:14:24
000069672 980__ $$aARTICLE