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

• DOI: 10.1073/pnas.2014442118
• Publication Date: 2021-01-12T10:47:53Z
• Authors: Nir Salinas; Einav Tayeb-Flige...; Massimo D. Sammito; Daniel Bloch; Raz Jelinek; Dror Noy; Isabel Usón; Meytal Landau
• Keywords: Amyloid (mycology)

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-α fibrils the amphibian antimicrobial peptide uperin 3.5 at atomic resolution, an architecture initially discovered in bacterial PSMα3 cytotoxin. The and comprised antiparallel parallel helical sheets, respectively, recapitulating properties β-sheets. Uperin demonstrated chameleon a secondary structure switch, forming mostly cross-β absence lipids. was largely induced by, formed on, cells or membrane mimetics, led damage cell death. These findings suggest regulation mechanism, includes storage inactive peptides well environmentally activation 3.5, via cross-α/β fibrils.