Stabilization effect of intrinsically disordered regions on multidomain proteins : The case of the methyl-cpg protein 2, mecp2
Ortega-Alarcon, D. (Universidad de Zaragoza. Instituto de Biocomputación y Física de Sistemas Complejos)
Claveria-Gimeno, R. (Instituto de Investigación Sanitaria de Aragón)
Vega, S. (Universidad de Zaragoza)
Jorge-Torres, Olga Caridad (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Esteller, M. (Universitat de Barcelona. Departament de Ciències Fisiològiques)
Abian, O. (Universidad de Zaragoza. Departamento de Bioquímica y Biología Molecular y Celular)
Velazquez-Campoy, A. (Gobierno de Aragón)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	Intrinsic disorder plays an important functional role in proteins. Disordered regions are linked to posttranslational modifications, conformational switching, extra/intracellular trafficking, and allosteric control, among other phenomena. Disorder provides proteins with enhanced plasticity, resulting in a dynamic protein conformational/functional landscape, with well-structured and disordered regions displaying reciprocal, interdependent features. Although lacking well-defined conformation, disordered regions may affect the intrinsic stability and functional properties of ordered regions. MeCP2, methyl-CpG binding protein 2, is a multifunctional transcriptional regulator associated with neuronal development and maturation. MeCP2 multidomain structure makes it a prototype for multidomain, multifunctional, intrinsically disordered proteins (IDP). The methyl-binding domain (MBD) is one of the key domains in MeCP2, responsible for DNA recognition. It has been reported previously that the two disordered domains flanking MBD, the N-terminal domain (NTD) and the intervening domain (ID), increase the intrinsic stability of MBD against thermal denaturation. In order to prove unequivocally this stabilization effect, ruling out any artifactual result from monitoring the unfolding MBD with a local fluorescence probe (the single tryptophan in MBD) or from driving the protein unfolding by temperature, we have studied the MBD stability by differential scanning calorimetry (reporting on the global unfolding process) and chemical denaturation (altering intramolecular interactions by a different mechanism compared to thermal denaturation).
Grants:	Ministerio de Economía y Competitividad CPII13/00017 Ministerio de Economía y Competitividad PI15/00663 Instituto de Salud Carlos III PI18/00349
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Biomolecules, Vol. 11 Núm. 8 (august 2021) , p. 1216, ISSN 2218-273X

DOI: 10.3390/biom11081216
PMID: 34439881

18 p, 2.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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