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oai:recercat.cat:2072/4408182026-03-13T06:53:37Zcom_2072_98col_2072_378192

The N-terminal helix controls the transition between the soluble and amyloid states of an FF domain Castillo Cano, Virginia Chiti, Fabrizio Ventura, Salvador Amyloid proteins Protein structure Fluorescence Urea Globular proteins Glycine Light scattering Protein structure prediction Background: Protein aggregation is linked to the onset of an increasing number of human nonneuropathic (either localized or systemic) and neurodegenerative disorders. In particular, misfolding of native α-helical structures and their self-assembly into nonnative intermolecular β-sheets has been proposed to trigger amyloid fibril formation in Alzheimer's and Parkinson's diseases. Methods: Here, we use a battery of biophysical techniques to elecidate the conformational conversion of native α-helices into amyloid fibrils using an all-α FF domain as a model system. - Results: we show that under mild denaturing conditions at low pH this FF domain self-assembles into amyloid fibrils. Theoretical and experimental dissection of the secondary structure elements in this domain indicates that the helix 1 at the N-terminus has both the highest α-helical and amyloid propensities, controlling the transition between soluble and aggregated states of the protein. - Conclusions: the data illustrates the overlap between the propensity to form native α-helices and amyloid structures in protein segments. Significance: The results presented contribute to explain why proteins cannot avoid the presence of aggregation-prone regions and indeed use stable α-helices as a strategy to neutralize such potentially deleterious stretches. 2013 Article https://ddd.uab.cat/record/225176 urn:10.1371/journal.pone.0058297 urn:oai:ddd.uab.cat:225176 urn:pmid:23505482 urn:scopus_id:84874738423 urn:articleid:19326203v8n3ae58297 urn:oai:egreta.uab.cat:publications/6fc32100-89ef-4208-8bba-714d150076fb urn:pmc-uid:3591442 urn:pmcid:PMC3591442 urn:oai:pubmedcentral.nih.gov:3591442 eng Ministerio de Ciencia e Innovación BFU2010-14901 Ministerio de Educación y Ciencia FPUAP2007-02849 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-760 PloS one ; Vol. 8 issue 3 (2013), art. e58297 open access 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. https://creativecommons.org/licenses/by/4.0/ application/pdf