The Cryo-EM structures of two amphibian antimicrobial cross-β amyloid fibrils

• DOI: 10.1038/s41467-022-32039-z
• Publication Date: 2022-07-27T21:04:02Z
• Authors: Robert Bücker; Carolin Seuring; Cornelia Cazey; Katharina Veith; Maria García-Alai; Kay Grünewald; Meytal Landau
• Keywords: Cryo-Electron Microscopy; Amyloid (mycology); Beta sheet

Abstract The amyloid-antimicrobial link hypothesis is based on antimicrobial properties found in human amyloids involved neurodegenerative and systemic diseases, along with amyloidal structural peptides (AMPs). Supporting this hypothesis, we here determined the fibril structure of two AMPs from amphibians, uperin 3.5 aurein 3.3, by cryogenic electron microscopy (cryo-EM), revealing amyloid cross-β fibrils mated β-sheets at atomic resolution. Uperin formed a 3-blade symmetrical propeller nine per layer including tight β-sheet interfaces. This cryo-EM complements cross-α conformation previously crystallography, substantiating secondary switch mechanism 3.5. 3.3 arrangement consisted six layer, all showing kinked allowing rounded compactness fibril. are similar to LARKS (Low-complexity, Amyloid-like, Reversible, Kinked Segments) functional amyloids.