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Cryo-EM demonstrates the in vitro proliferation of an ex vivo amyloid fibril morphology by seeding

Author

Listed:
  • Thomas Heerde

    (Institute of Protein Biochemistry, Ulm University)

  • Matthies Rennegarbe

    (Institute of Protein Biochemistry, Ulm University)

  • Alexander Biedermann

    (Institute of Protein Biochemistry, Ulm University)

  • Dilan Savran

    (Max-Planck-Institute of Biophysics)

  • Peter B. Pfeiffer

    (Institute of Protein Biochemistry, Ulm University)

  • Manuel Hitzenberger

    (Technical University of Munich)

  • Julian Baur

    (Institute of Protein Biochemistry, Ulm University)

  • Ioana Puscalau-Girtu

    (Institute of Protein Biochemistry, Ulm University)

  • Martin Zacharias

    (Technical University of Munich)

  • Nadine Schwierz

    (Max-Planck-Institute of Biophysics)

  • Christian Haupt

    (Institute of Protein Biochemistry, Ulm University)

  • Matthias Schmidt

    (Institute of Protein Biochemistry, Ulm University)

  • Marcus Fändrich

    (Institute of Protein Biochemistry, Ulm University)

Abstract

Several studies showed that seeding of solutions of monomeric fibril proteins with ex vivo amyloid fibrils accelerated the kinetics of fibril formation in vitro but did not necessarily replicate the seed structure. In this research we use cryo-electron microscopy and other methods to analyze the ability of serum amyloid A (SAA)1.1-derived amyloid fibrils, purified from systemic AA amyloidosis tissue, to seed solutions of recombinant SAA1.1 protein. We show that 98% of the seeded fibrils remodel the full fibril structure of the main ex vivo fibril morphology, which we used for seeding, while they are notably different from unseeded in vitro fibrils. The seeded fibrils show a similar proteinase K resistance as ex vivo fibrils and are substantially more stable to proteolytic digestion than unseeded in vitro fibrils. Our data support the view that the fibril morphology contributes to determining proteolytic stability and that pathogenic amyloid fibrils arise from proteolytic selection.

Suggested Citation

  • Thomas Heerde & Matthies Rennegarbe & Alexander Biedermann & Dilan Savran & Peter B. Pfeiffer & Manuel Hitzenberger & Julian Baur & Ioana Puscalau-Girtu & Martin Zacharias & Nadine Schwierz & Christia, 2022. "Cryo-EM demonstrates the in vitro proliferation of an ex vivo amyloid fibril morphology by seeding," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27688-5
    DOI: 10.1038/s41467-021-27688-5
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    Cited by:

    1. 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.
    2. Sambhasan Banerjee & Julian Baur & Christoph Daniel & Peter Benedikt Pfeiffer & Manuel Hitzenberger & Lukas Kuhn & Sebastian Wiese & Johan Bijzet & Christian Haupt & Kerstin U. Amann & Martin Zacharia, 2022. "Amyloid fibril structure from the vascular variant of systemic AA amyloidosis," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

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