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cc-by (c)  Ortega-Alarcon, D. et al., 2021
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/221658

Stabilization effect of intrinsically disordered regions on multidomain proteins: The case of the methyl-CpG protein 2, MeCP2

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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).

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ORTEGA ALARCÓN, David, et al. Stabilization effect of intrinsically disordered regions on multidomain proteins: The case of the methyl-CpG protein 2, MeCP2. Biomolecules. 2021. Vol. 11, num. 8. ISSN 2218-273X. [consulted: 11 of June of 2026]. Available at: https://hdl.handle.net/2445/221658

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