Structure-function Relationships in fibril forming Antimicrobial peptide
Amyloid-like fibrils formed by antimicrobial peptides (AMPs) and microbial toxins hold significant promise as novel antimicrobial therapeutics and targets for antivirulence strategies. This study explores the relationship between amyloidogenic and antimicrobial properties, shedding light on the structural diversity and functional implications of these self-assembled biomaterials. Our laboratory previously discovered the cross-α amyloid conformation, which is uniquely different from the established amyloid structure associated with the cross-β conformation. Furthermore, the lab discovered a unique ‘chameleon’-like behavior in fibril polymorphism of several AMPs, showing a secondary structure switch from cross-β to cross-α configurations, often induced by exposure to bacterial membranes. This suggests a highly adaptive regulation mechanism. To identify more such chameleon toxic peptides, computational tools were developed by Peleg RagonisBachar (sequence-based) and Itai Bloch (structure-based). Candidate sequences were tested and characterized by experimental investigations. The experimental results corroborate the predictive capabilities of the computational tools developed, allowing us to identify dozens of toxic sequences that form fibrils, which led to high resolution structure determination and structure-function relationship studies. This work offers novel insights into the design and characterization of AMPs and virulence factors with amyloidogenic features.
