Uperin antimicrobial peptides: Structures, activity, and amyloid fibril formation

Australian native anuran antimicrobial peptides from the uperin family, particularly uperin 3.5, have been investigated for their ability to form amyloid fibrils. Variants of uperin peptides with alterations in their charge, in particular the removal of positive charge, significantly affect uperin amyloid fibril-forming propensity and antimicrobial activity. Positive charge is also a major determinant on the interaction of uperin 3.5 with membranes. Molecular dynamics simulations have provided insight into the initial stages of uperin 3.5 aggregation to form amyloid fibrils. Uperin 3.5 possesses chameleon-like properties whereby it can adopt either the cross-β or the unusual cross-α amyloid fibrillar conformation, depending on solution conditions. Investigating the aggregation and antimicrobial properties of uperin peptides may assist in understanding the etiology of amyloidosis conditions such as Alzheimer's disease, and in developing therapeutics for their treatment.