Expanding the amyloid landscape: structural plasticity of antimicrobial peptides

Le résumé fourni par la source

Amyloid formation is increasingly recognized as a functional property of antimicrobial and virulence-associated peptides, yet the relationship between peptide assembly, structure, and biological activity remains poorly understood. Here, we combined computational prediction with biophysical, functional, native mass spectrometry, and cryo-EM analyses to identify fifteen previously unrecognized fibril-forming peptides and define their assembly landscapes. Most peptides displayed pronounced structural plasticity, undergoing environmentally induced transitions between α-helical and β-rich conformations. High-resolution cryo-EM structures of aurein 1.2 and brevinin-1OKc revealed multiple polymorphic cross-β architectures, including a distinctive radially symmetric six-pointed assembly, while native mass spectrometry uncovered fundamentally different oligomerization pathways despite convergence on cross-β fibrillar endpoints. Together, these findings support a model in which biological activity is governed not by a single structural endpoint but by transitions across a dynamic assembly landscape containing multiple accessible amyloid states and soluble intermediates. Our results establish structural plasticity as a defining feature of antimicrobial and virulence-associated peptides and suggest that environmentally regulated transitions across an amyloid assembly landscape provide a mechanism for rapid functional adaptation.

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