Unravelling the Amyloidogenic Properties of Uperin 3.5 and 3.7 Variants through Biophysical Investigations

Amyloidosis is a disease characterized by the accumulation of misfolded proteins, leading to the formation of amyloid fibrils that deposit in tissues and disrupt normal organ physiology. Proteins and peptides can form amyloids through changes in their physiological environment. Recent studies have suggested that amyloid beta (Aβ), known for its role in neurodegenerative diseases like Alzheimer's and Parkinson's, may also have antimicrobial properties. The net charge of antimicrobial peptides (AMPs) influences their activity against microbes, with the charge-to-hydrophobicity ratio playing a role. The Uperin peptides from Australian toadlets have shown antimicrobial activity and can self-assemble into amyloids. The findings of this study highlight the importance of specific amino acid residues, overall charge, and functional groups in the biophysical behaviours of Uperin 3.5 (U3.5) and Uperin 3.7 (U3.7) peptides.