Common features in the unfolding and misfolding of PDZ domains and beyond : the modulatory effect of domain swapping and extra-elements
Murciano Calles, Javier (Universidad de Granada. Departamento de Química Física)
Güell Bosch, Jofre (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Villegas Hernández, Sandra (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Martínez, José C. (Universidad de Granada. Departamento de Química Física)

Data:	2016
Resum:	PDZ domains are protein-protein interaction modules sharing the same structural arrangement. To discern whether they display common features in their unfolding/misfolding behaviour we have analyzed in this work the unfolding thermodynamics, together with the misfolding kinetics, of the PDZ fold using three archetypical examples: the second and third PDZ domains of the PSD95 protein and the Erbin PDZ domain. Results showed that all domains passed through a common intermediate, which populated upon unfolding, and that this in turn drove the misfolding towards worm-like fibrillar structures. Thus, the unfolding/misfolding behaviour appears to be shared within these domains. We have also analyzed how this landscape can be modified upon the inclusion of extra-elements, as it is in the nNOS PDZ domain, or the organization of swapped species, as happens in the second PDZ domain of the ZO2 protein. Although the intermediates still formed upon thermal unfolding, the misfolding was prevented to varying degrees.
Ajuts:	Ministerio de Economía y Competitividad BIO2012-39922-C02 Instituto de Salud Carlos III PI13-01330 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-0761
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Amino Acid Sequence ; Calorimetry, Differential Scanning ; Models, Molecular ; PDZ Domains ; Protein Conformation ; Protein Folding ; Protein Unfolding ; Spectroscopy, Fourier Transform Infrared
Publicat a:	Scientific reports, Vol. 6 (January 2016) , art. 19242, ISSN 2045-2322

DOI: 10.1038/srep19242
PMID: 26754462

7 p, 899.7 KB

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