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

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  • Robert Bücker

    (Centre for Structural Systems Biology
    University of Hamburg
    Rigaku Europe SE
    Leibniz Institute of Virology)

  • Carolin Seuring

    (Centre for Structural Systems Biology
    University of Hamburg
    Leibniz Institute of Virology)

  • Cornelia Cazey

    (Centre for Structural Systems Biology
    University of Hamburg)

  • Katharina Veith

    (European Molecular Biology Laboratory, EMBL Hamburg)

  • Maria García-Alai

    (Centre for Structural Systems Biology
    European Molecular Biology Laboratory, EMBL Hamburg)

  • Kay Grünewald

    (Centre for Structural Systems Biology
    University of Hamburg
    Leibniz Institute of Virology
    University of Oxford)

  • Meytal Landau

    (Centre for Structural Systems Biology
    European Molecular Biology Laboratory, EMBL Hamburg
    Technion-Israel Institute of Technology)

Abstract

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

Suggested Citation

  • Robert Bücker & Carolin Seuring & Cornelia Cazey & Katharina Veith & Maria García-Alai & Kay Grünewald & Meytal Landau, 2022. "The Cryo-EM structures of two amphibian antimicrobial cross-β amyloid fibrils," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32039-z
    DOI: 10.1038/s41467-022-32039-z
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    References listed on IDEAS

    as
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