Identification of fibril-forming antimicrobial peptides reveals structural plasticity and diverse amyloid architectures

Amyloid formation, in which peptides and proteins self-assemble into ordered fibrils, is increasingly recognized as a functional property of antimicrobial and virulence-associated peptides. However, how widespread these assemblies are and how their structures relate to biological activity remain unclear. Here we show that computationally selected antimicrobial and virulence-associated peptides frequently form fibrils and can access multiple, environmentally regulated structural states. Many peptides switched between α-helical and β-rich conformations in response to changes in their environment. High-resolution cryogenic electron microscopy of aurein 1.2 and brevinin-1OKc revealed polymorphic cross-β amyloid structures, including kinked peptide chains and a radially symmetric six-chain architecture. Native mass spectrometry further revealed distinct assembly pathways: aurein 1.2 accumulated soluble oligomeric intermediates, whereas brevinin-1OKc remained predominantly monomeric before fibril formation. Together, these findings expand the known structural repertoire of antimicrobial amyloids and suggest that structural plasticity and alternative assembly pathways enable antimicrobial peptides to respond dynamically to their biological environment.