The N-terminal helix controls the transition between the soluble and amyloid states of an FF domain
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 prop...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2013 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:225176 |
| Acceso en línea: | https://ddd.uab.cat/record/225176 https://dx.doi.org/urn:doi:10.1371/journal.pone.0058297 |
| Access Level: | acceso abierto |
| Palabra clave: | Amyloid proteins Protein structure Fluorescence Urea Globular proteins Glycine Light scattering Protein structure prediction |
| Sumario: | 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. |
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