Influence of the disordered domain structure of MeCP2 on its structural stability and dsDNA interaction

Ortega-Alarcon, D. (Universidad de Zaragoza) ; Claveria-Gimeno, R. ; Vega, S. ; Jorge-Torres, O.C. ; Esteller, M. ; Abian, O. (Universidad de Zaragoza) ; Velazquez-Campoy, A. (Universidad de Zaragoza)

Resumen: Methyl-CpG binding protein 2 (MeCP2) is a transcriptional regulator and a chromatin-associated structural protein. MeCP2 deregulation results in two neurodevelopmental disorders: MeCP2 dysfunction is associated with Rett syndrome, while excess of activity is associated with MeCP2 duplication syndrome. MeCP2 is an intrinsically disordered protein (IDP) constituted by six structural domains with variable, small percentage of well-defined secondary structure. Two domains, methyl-CpG binding domain (MBD) and transcription repressor domain (TRD), are the elements responsible for dsDNA binding ability and recruitment of the gene transcription/silencing machinery, respectively. Previously we studied the influence of the completely disordered, MBD-flanking domains (N-terminal domain, NTD, and intervening domain, ID) on the structural and functional features of the MBD (Claveria-Gimeno, R. et al. Sci Rep. 2017, 7, 41, 635). Here we report the biophysical study of the influence of the remaining domains (transcriptional repressor domain, TRD, and C-terminal domains, CTDa and CTDß) on the structural stability of MBD and the dsDNA binding capabilities of MBD and ID. The influence of distant disordered domains on MBD properties makes it necessary to consider the NTD-MBD-ID variant as the minimal protein construct for studying dsDNA/chromatin binding properties, while the full-length protein should be considered for transcriptional regulation studies.

Idioma: Inglés

DOI: 10.1016/j.ijbiomac.2021.01.206

Año: 2021

Publicado en: International journal of biological macromolecules 175 (2021), 58-66
ISSN: 0141-8130

Factor impacto JCR: 8.025 (2021)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 46 / 297 = 0.155 (2021) - Q1 - T1
Categ. JCR: POLYMER SCIENCE rank: 6 / 90 = 0.067 (2021) - Q1 - T1
Categ. JCR: CHEMISTRY, APPLIED rank: 8 / 72 = 0.111 (2021) - Q1 - T1

Factor impacto CITESCORE: 11.6 - Medicine (Q1) - Biochemistry, Genetics and Molecular Biology (Q1)

Factor impacto SCIMAGO: 1.1 - Biochemistry (Q1) - Economics and Econometrics (Q1) - Structural Biology (Q1) - Molecular Biology (Q1) - Energy (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B25-17R
Financiación: info:eu-repo/grantAgreement/ES/DGA/E45-17R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI15-00663-Investing in your future
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BFU2016-78232-P

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)