Interactions of Amyloid Fibrils with Functional Proteins: Modulating Effect of Polyphenols

Abstract

The elucidation of interactions between functional proteins and amyloid fibrils is crucial for understanding the molecular basis of amyloid diseases, which are characterized by protein misfolding and aggregation. Polyphenols, due to their diverse biological properties, have garnered attention for their potential to modulate these protein-fibril interactions, thereby influencing disease progression and offering therapeutic possibilities. In this study, we investigated the effects of quercetin and its binary combinations with other polyphenols on the binding affinity between cytochrome c, in both its reduced and oxidized forms, and amyloid fibrils of insulin and apolipoprotein A-I. Our results demonstrate that quercetin complexation with cytochrome c decreases the binding affinity of insulin fibrils for both forms of the protein, while increasing the affinity for apolipoprotein A-I fibrils. This modulation was attributed to competitive or allosteric effects exerted by quercetin on cytochrome c. Additionally, while binary combinations of quercetin with other polyphenols did not reduce the affinity of insulin fibrils for oxidized cytochrome c, they did decrease the affinity in the case of reduced counterpart. These findings highlight the selective and significant impact of polyphenolic compounds on the interactions between amyloid fibrils and functional proteins, suggesting potential pathways for therapeutic intervention in amyloid-related disorders.

Keywords

• amyloid fibrils
• functional proteins
• polyphenols
• molecular docking