title: Morphology of self-assembled structures formed by short peptides from the amyloidogenic protein tau depends on the solvent in which the peptides are dissolved.
abstract: The aggregation behavior of peptides Ac-VQIVYK-amide (AcPHF6) and Ac-QIVYK-amide (AcPHF5) from the amyloidogenic protein tau was examined by atomic force microscopy (AFM) and fluorescence microscopy. Although AcPHF5 did not show enhancement of thioflavin T (ThT) fluorescence in aqueous buffer, distinct aggregates were discernible when peptide was dissolved in organic solvents such as methanol (MeOH), trifluoroethanol (TFE), and hexafluoroisopropanol (HFIP) dried on mica and examined by AFM. Self-association was evident even though the peptide did not have the propensity to form secondary structures in the organic solvents. In dried films, the peptide adopts predominantly beta-conformation which results in the formation of distinct aggregates. ThT fluorescence spectra and fluorescence images indicate the formation of fibrils when AcPHF6 solutions in organic solvents were diluted into buffer. AcPHF6 had the ability to organize into fibrillar structures when AFM samples were prepared from peptide dissolved in MeOH, TFE, HFIP, and also when diluted into buffer. AcPHF6 showed propensity for beta-structure in aqueous buffer. In MeOH and TFE, AcPHF6 showed helical and beta-structure. Morphology of the fibrils was dependent on peptide conformation in the organic solvents. The structures observed for AcPHF6 are formed rapidly and long incubation periods in the solvents are not necessary. The structures with varying morphologies observed for AcPHF5 and AcPHF6 appear to be mediated by surfaces such as mica and the organic solvents used for dissolution of the peptides.
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, Andhra Pradesh, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Chaudhary
authors.forename: Shashi
authors.initials: S
authors.lastname: Singh
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Nagaraj
mesh_terms: D052160:Benzothiazoles; D002942:Circular Dichroism; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000737:chemistry; D020005:Propanols; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013844:Thiazoles; D014270:Trifluoroethanol; D016875:tau Proteins / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated
chemical_list: D052160:Benzothiazoles; D010446:Peptide Fragments; D020005:Propanols; D012997:Solvents; D013844:Thiazoles; D014270:Trifluoroethanol; D016875:tau Proteins; C009462:thioflavin T; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated