The amphibian antimicrobial peptide uperin 3.5 is a cross-α/cross-β chameleon functional amyloid

Antimicrobial activity is being increasingly linked to amyloid fibril formation, suggesting physiological roles for some human amyloids, which have historically been viewed as strictly pathological agents. This work reports on formation of functional cross-a amyloid fibrils of the amphibian antimicrobial peptide uperin 3.5 at atomic resolution, an architecture initially discovered in the bacterial PSM alpha 3 cytotoxin. The fibrils of uperin 3.5 and PSMa3 comprised antiparallel and parallel helical sheets, respectively, recapitulating properties of beta-sheets. Uperin 3.5 demonstrated chameleon properties of a secondary structure switch, forming mostly cross-beta fibrils in the absence of lipids. Uperin 3.5 helical fibril formation was largely induced by, and formed on, bacterial cells or membrane mimetics, and led to membrane damage and cell death. These findings suggest a regulation mechanism, which includes storage of inactive peptides as well as environmentally induced activation of uperin 3.5, via chameleon cross-alpha/beta amyloid fibrils.

Automated summary

The study found that two subtypes of antimicrobial peptide uperin 3.5 can form functional amyloid fibrils, which has important physiological implications. Uperin 3.5 mainly forms cross-beta fibrils in the absence of lipids, but helical fibril formation is induced by bacterial cells or membrane mimetics, leading to membrane damage and cell death.