Recent studies have found that β-amyloid (Aβ) oligomers may play much more important roles than amyloid plaques in the pathogenesis of Alzheimer's disease (AD). However, due to the complexity of Aβ, studying the structural basis of Aβ oligomer toxicity is challenging. Here, we assessed the amphiphilic property and β-hairpin structure of Aβ monomer. The potential impacts of Aβ oligomers and three sequence-modifying peptides on the enzyme activities of horseradish peroxidase (HRP) and alkaline phosphatase (ALP) were further evaluated. We demonstrated that Aβ oligomer possesses the ability to alter the activity of two enzymes. Moreover, modifications on the hydrophobic region and β-turn structure of Aβ monomer significantly alter its impacts on the enzyme activities. In addition, these modifications also change the bonding modes of Aβ monomers or oligomers binding to HRP, as assessed by molecular docking. All of these findings provide direct experimental evidence to reveal the critical roles of the amphiphilic property and β-sheet structure of Aβ monomer in its impacts on protein activity.
Keywords: Alzheimer’s disease; hydrophobic region; β-amyloid; β-hairpin structure; β-turn.