Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
AbstractAmyloid 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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Marinelli, P.; Castillo, V.; Ventura, S. Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain. Int. J. Mol. Sci. 2013, 14, 17830-17844.
Marinelli P, Castillo V, Ventura S. Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain. International Journal of Molecular Sciences. 2013; 14(9):17830-17844.Chicago/Turabian Style
Marinelli, Patrizia; Castillo, Virginia; Ventura, Salvador. 2013. "Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain." Int. J. Mol. Sci. 14, no. 9: 17830-17844.