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Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain

Amyloid fibril formation is implicated in different human diseases. The transition between native α-helices and nonnative intermolecular β-sheets has been suggested to be a trigger of fibrillation in different conformational diseases. The FF domain of the URN1 splicing factor (URN1-FF) is a small al...

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Autores principales: Marinelli, Patrizia, Castillo, Virginia, Ventura, Salvador
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794755/
https://www.ncbi.nlm.nih.gov/pubmed/23999589
http://dx.doi.org/10.3390/ijms140917830
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author Marinelli, Patrizia
Castillo, Virginia
Ventura, Salvador
author_facet Marinelli, Patrizia
Castillo, Virginia
Ventura, Salvador
author_sort Marinelli, Patrizia
collection PubMed
description Amyloid fibril formation is implicated in different human diseases. The transition between native α-helices and nonnative intermolecular β-sheets has been suggested to be a trigger of fibrillation in different conformational diseases. The FF domain of the URN1 splicing factor (URN1-FF) is a small all-α protein that populates a molten globule (MG) at low pH. Despite the fact that this conformation maintains most of the domain native secondary structure, it progressively converts into β-sheet enriched and highly ordered amyloid fibrils. In this study, we investigated if 2,2,2-trifluoroethanol (TFE) induced conformational changes that affect URN1-FF amyloid formation. Despite TFE having been shown to induce or increase the aggregation of both globular and disordered proteins at moderate concentrations, we demonstrate here that in the case of URN1-FF it reinforces its intrinsic α-helical structure, which competes the formation of aggregated assemblies. In addition, we show that TFE induces conformational diversity in URN1-FF fibrils, in such a way that the fibrils formed in the presence and absence of the cosolvent represent different polymorphs. It is suggested that the effect of TFE on both the soluble and aggregated states of URN1-FF depends on its ability to facilitate hydrogen bonding.
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spelling pubmed-37947552013-10-21 Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain Marinelli, Patrizia Castillo, Virginia Ventura, Salvador Int J Mol Sci Article Amyloid fibril formation is implicated in different human diseases. The transition between native α-helices and nonnative intermolecular β-sheets has been suggested to be a trigger of fibrillation in different conformational diseases. The FF domain of the URN1 splicing factor (URN1-FF) is a small all-α protein that populates a molten globule (MG) at low pH. Despite the fact that this conformation maintains most of the domain native secondary structure, it progressively converts into β-sheet enriched and highly ordered amyloid fibrils. In this study, we investigated if 2,2,2-trifluoroethanol (TFE) induced conformational changes that affect URN1-FF amyloid formation. Despite TFE having been shown to induce or increase the aggregation of both globular and disordered proteins at moderate concentrations, we demonstrate here that in the case of URN1-FF it reinforces its intrinsic α-helical structure, which competes the formation of aggregated assemblies. In addition, we show that TFE induces conformational diversity in URN1-FF fibrils, in such a way that the fibrils formed in the presence and absence of the cosolvent represent different polymorphs. It is suggested that the effect of TFE on both the soluble and aggregated states of URN1-FF depends on its ability to facilitate hydrogen bonding. MDPI 2013-08-30 /pmc/articles/PMC3794755/ /pubmed/23999589 http://dx.doi.org/10.3390/ijms140917830 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Marinelli, Patrizia
Castillo, Virginia
Ventura, Salvador
Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
title Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
title_full Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
title_fullStr Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
title_full_unstemmed Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
title_short Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
title_sort trifluoroethanol modulates amyloid formation by the all α-helical urn1 ff domain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794755/
https://www.ncbi.nlm.nih.gov/pubmed/23999589
http://dx.doi.org/10.3390/ijms140917830
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