Peptide sequence modulates amyloid fibril formation and triggers Alzheimer's disease. The N-terminal region of amyloid peptide is disordered and lack any specific secondary structure. An ionic interaction of Aβ1-11 with factor XII is critical for the activation of the contact system in Alzheimer's disease. In this study, we report the self-assembly of fluctuating N-terminal Aβ1-11 into nanotubes using atomic force micrography, transmission electron microscopy, circular dichroism studies and molecular modeling studies. The effect of four polyphenols: baicalein, rutin, vanillin and cyanidin-3-O-glucoside (C3G) was also explored on the amyloid fibril inhibitor perspective using amyloid specific dye Thioflavin T (ThT). AFM micrographs suggested the self-assembly of Aβ1-11 into nanotubes after three weeks of incubation. Microwave treatment results in the conformational variation of disordered structure to β-sheet rich amyloid fibrils. The presence of salts (sodium and potassium chloride) induces the structural transformation of Aβ1-11 to super-helix. Fluorescence spectroscopy studies using ThT suggested differential inhibition of amyloid fibrils formation in the presence of polyphenols. Molecular modeling studies suggested that binding of polyphenols to Aβ1-11 through hydrophobic interaction (Phe4 and Tyr 10) and hydrogen bonding (Glu3 and Arg5) play a substantial role in stabilizing Aβ1-11-polyphenols complex. In the presence of polyphenols, Aβ1-11 transforms to hybrid nanostructures thus hindering amyloid fibril formation. These results provide structural insights and importance of the N-terminal residues in the Aβ1-42 self-assembly mechanism.
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