Carregant...
Miniatura

Tipus de document

Article

Versió

Versió acceptada

Data de publicació

Llicència de publicació

cc-by-nc-nd (c) Ortega Alarcón et. al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/175234

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

Títol de la revista

Director/Tutor

ISSN de la revista

Títol del volum

Resum

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, CTDα and CTDβ) 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.

Citació

Citació

ORTEGA ALARCÓN, David, CLAVERÍA GIMENO, Rafael, VEGA, Sonia, JORGE-TORRES, Olga c., ESTELLER, Manel, ABIAN, Olga, VELÁZQUEZ-CAMPOY, Adrián. Influence of the disordered domain structure of MeCP2 on its structural stability and dsDNA interaction. _International Journal of Biological Macromolecules_. 2021. Vol. 175, núm. 58-66. [consulta: 15 de gener de 2026]. ISSN: 0141-8130. [Disponible a: https://hdl.handle.net/2445/175234]

Exportar metadades

JSON - METS

Compartir registre