title: Self-Assembly of Aβ40, Aβ42 and Aβ43 Peptides in Aqueous Mixtures of Fluorinated Alcohols.
abstract: Fluorinated alcohols such as hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE) have the ability to promote α-helix and β-hairpin structure in proteins and peptides. HFIP has been used extensively to dissolve various amyloidogenic proteins and peptides including Aβ, in order to ensure their monomeric status. In this paper, we have investigated the self-assembly of Aβ40, Aβ42, and Aβ43 in aqueous mixtures of fluorinated alcohols from freshly dissolved stock solutions in HFIP. We have observed that formation of fibrillar and non-fibrillar structures are dependent on the solvent composition. Peptides form fibrils with ease when reconstituted in deionized water from freshly dissolved HFIP stocks. In aqueous mixtures of fluorinated alcohols, either predominant fibrillar structures or clustered aggregates were observed. Aqueous mixtures of 20% HFIP are more favourable for Aβ fibril formation as compared to 20% TFE. When Aβ40, Aβ42, and Aβ43 stocks in HFIP are diluted in 50% aqueous mixtures in phosphate buffer or deionized water followed by slow evaporation of HFIP, Aβ peptides form fibrils in phosphate buffer and deionized water. The clustered structures could be off-pathway aggregates. Aβ40, Aβ42, and Aβ43 showed significant α-helical content in freshly dissolved HFIP stocks. The α-helical conformational intermediate in Aβ40, Aβ42, and Aβ43 could favour the formation of both fibrillar and non-fibrillar aggregates depending on solvent conditions and rate of α-helical to β-sheet transition.
authors: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India.
authors: Sanjai Kumar
authors: SK
authors: Pachahara
authors: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India.
authors: Harikrishna
authors: H
authors: Adicherla
authors: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India.
authors: Ramakrishnan
authors: R
authors: Nagaraj
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D054879:Halogenation; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000737:chemistry*; D020005:Propanols / Q000737:chemistry*; D011487:Protein Conformation; D012997:Solvents; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D014270:Trifluoroethanol / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D020005:Propanols; D012997:Solvents; D014270:Trifluoroethanol; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C098994:amyloid beta-protein (1-43); C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated