000097131 001__ 97131
000097131 005__ 20230921135436.0
000097131 0247_ $$2doi$$a10.3390/biom10111533
000097131 0248_ $$2sideral$$a121079
000097131 037__ $$aART-2020-121079
000097131 041__ $$aeng
000097131 100__ $$0(orcid)0000-0003-1885-4365$$aOrtega-Alarcon, D.$$uUniversidad de Zaragoza
000097131 245__ $$aMolecular context-dependent effects induced by rett syndrome-associated mutations in mecp2
000097131 260__ $$c2020
000097131 5060_ $$aAccess copy available to the general public$$fUnrestricted
000097131 5203_ $$aMethyl-CpG binding protein 2 (MeCP2) is a transcriptional regulator and a chromatinbinding protein involved in neuronal development and maturation. Loss-of-function mutations in MeCP2 result in Rett syndrome (RTT), a neurodevelopmental disorder that is the main cause of mental retardation in females. MeCP2 is an intrinsically disordered protein (IDP) constituted by six domains. Two domains are the main responsible elements for DNA binding (methyl-CpG binding domain, MBD) and recruitment of gene transcription/silencing machinery (transcription repressor domain, TRD). These two domains concentrate most of the RTT-associated mutations. R106W and R133C are associated with severe and mild RTT phenotype, respectively. We have performed a comprehensive characterization of the structural and functional impact of these substitutions at molecular level. Because we have previously shown that the MBD-flanking disordered domains (Nterminal domain, NTD, and intervening domain, ID) exert a considerable influence on the structural and functional features of the MBD (Claveria-Gimeno, R. et al. Sci Rep. 2017, 7, 41635), here we report the biophysical study of the influence of the protein scaffold on the structural and functional effect induced by these two RTT-associated mutations. These results represent an example of how a given mutation may show different effects (sometimes opposing effects) depending on the molecular context.
000097131 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-17R$$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017$$9info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI15-00663-Investing in your future$$9info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BFU2016-78232-P
000097131 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000097131 590__ $$a4.879$$b2020
000097131 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b96 / 296 = 0.324$$c2020$$dQ2$$eT1
000097131 592__ $$a1.125$$b2020
000097131 593__ $$aMolecular Biology$$c2020$$dQ2
000097131 593__ $$aBiochemistry$$c2020$$dQ2
000097131 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000097131 700__ $$aClaveria-Gimeno, R.
000097131 700__ $$0(orcid)0000-0002-1232-6310$$aVega, S.
000097131 700__ $$aJorge-Torres, O.C.
000097131 700__ $$aEsteller, M.
000097131 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, O.$$uUniversidad de Zaragoza
000097131 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, A.$$uUniversidad de Zaragoza
000097131 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000097131 773__ $$g10, 11 (2020), 1533 [19 pp]$$tBiomolecules$$x2218-273X
000097131 8564_ $$s582299$$uhttps://zaguan.unizar.es/record/97131/files/texto_completo.pdf$$yVersión publicada
000097131 8564_ $$s463279$$uhttps://zaguan.unizar.es/record/97131/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000097131 909CO $$ooai:zaguan.unizar.es:97131$$particulos$$pdriver
000097131 951__ $$a2023-09-21-13:31:03
000097131 980__ $$aARTICLE