The N-terminal helix controls the transition between the soluble and amyloid states of an FF domain
Castillo Cano, Virginia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Chiti, Fabrizio (Università di Firenze. Dipartimento di Scienze Biochimiche)
Ventura, Salvador (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Fecha:	2013
Resumen:	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.
Ayudas:	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
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Amyloid proteins ; Protein structure ; Fluorescence ; Urea ; Globular proteins ; Glycine ; Light scattering ; Protein structure prediction
Publicado en:	PloS one, Vol. 8 issue 3 (2013) , art. e58297, ISSN 1932-6203

DOI: 10.1371/journal.pone.0058297
PMID: 23505482

15 p, 1.9 MB

El registro aparece en las colecciones:
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)
Artículos > Artículos de investigación
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