PH-dependent aggregation in intrinsically disordered proteins is determined by charge and lipophilicity
Santos Suárez, Jaime (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Iglesias, Valentin (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Mangiagalli, Marco (Department of Biotechnology and Biosciences, University of Milano-Bicocca)
Santos-Suárez, Juan (Galicia Supercomputing Center (CESGA))
Brocca, Stefania (Department of Biotechnology and Biosciences, University of Milano-Bicocca)
Pallarès i Goitiz, Irantzu (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ventura, Salvador (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Fecha:	2020
Resumen:	Protein aggregation is associated with an increasing number of human disorders and premature aging. Moreover, it is a central concern in the manufacturing of recombinant proteins for biotechnological and therapeutic applications. Nevertheless, the unique architecture of protein aggregates is also exploited by nature for functional purposes, from bacteria to humans. The relevance of this process in health and disease has boosted the interest in understanding and controlling aggregation, with the concomitant development of a myriad of algorithms aimed to predict aggregation propensities. However, most of these programs are blind to the protein environment and, in particular, to the influence of the pH. Here, we developed an empirical equation to model the pH-dependent aggregation of intrinsically disordered proteins (IDPs) based on the assumption that both the global protein charge and lipophilicity depend on the solution pH. Upon its parametrization with a model IDP, this simple phenomenological approach showed unprecedented accuracy in predicting the dependence of the aggregation of both pathogenic and functional amyloidogenic IDPs on the pH. The algorithm might be useful for diverse applications, from large-scale analysis of IDPs aggregation properties to the design of novel reversible nanofibrillar materials.
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Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Intrinsically disordered proteins ; Protein aggregation ; Protein solubility ; Amyloids ; Bioinformatics
Publicado en:	Cells, Vol. 9 (2020) , ISSN 2073-4409

DOI: 10.3390/cells9010145
PMID: 31936201

14 p, 2.0 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Instituto de Biotecnología y de Biomedicina (IBB)
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