The influence of H-bonding network disruption on morphology, structure and autofluorescence of amyloids.

Abstract

Hydrogen bonding plays a pivotal role in amyloid structures. The characteristic feature of amyloids is the presence of a secondary β-sheet structure in which hydrogen bonds are regularly aligned. Previous reports suggested that hydrogen bonds can be involved in the autofluorescence phenomenon of amyloids. Here, we studied a fragment of amyloidogenic amyloid-β (Aβ) peptide, Aβ(35-42), and its analogue with one ester bond replacing an amide, depsiAβ(35-42), to isolate the effect of disrupting the hydrogen bonding network on autofluorescence. We have chosen these sequences because they are lacking aromatic amino acids and contain α-amino and α-carboxyl groups at their N- and C-termini that can undergo protonation and deprotonation. Morphological characterization indicated that under acidic conditions (pH ∼2) Aβ(35-42) rapidly assembles into amyloid fibrils, whereas depsiAβ(35-42) forms spherical aggregates. The presence of a secondary β-sheet structure was confirmed in both samples. Interestingly, the autofluorescence signal was detected in depsiAβ(35-42) despite the absence of fibrillar structures, and its intensity was similar to that of Aβ(35-42). Furthermore, our studies revealed that the autofluorescence is pH-dependent. Overall, our results corroborate the hypothesis that proton transfer between the N- and C-termini of an aggregated peptide in β-sheet conformation is critical for its intrinsic fluorescence properties.