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Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids

Author

Listed:
  • Falk Liberta

    (Ulm University)

  • Sarah Loerch

    (Howard Hughes Medical Institute)

  • Matthies Rennegarbe

    (Ulm University)

  • Angelika Schierhorn

    (Martin-Luther-University)

  • Per Westermark

    (Uppsala University)

  • Gunilla T. Westermark

    (Uppsala University)

  • Bouke P. C. Hazenberg

    (University of Groningen, University Medical Center Groningen)

  • Nikolaus Grigorieff

    (Howard Hughes Medical Institute)

  • Marcus Fändrich

    (Ulm University)

  • Matthias Schmidt

    (Ulm University)

Abstract

Systemic AA amyloidosis is a worldwide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from the acute phase protein serum amyloid A. Here, we report the purification and electron cryo-microscopy analysis of amyloid fibrils from a mouse and a human patient with systemic AA amyloidosis. The obtained resolutions are 3.0 Å and 2.7 Å for the murine and human fibril, respectively. The two fibrils differ in fundamental properties, such as presence of right-hand or left-hand twisted cross-β sheets and overall fold of the fibril proteins. Yet, both proteins adopt highly similar β-arch conformations within the N-terminal ~21 residues. Our data demonstrate the importance of the fibril protein N-terminus for the stability of the analyzed amyloid fibril morphologies and suggest strategies of combating this disease by interfering with specific fibril polymorphs.

Suggested Citation

  • Falk Liberta & Sarah Loerch & Matthies Rennegarbe & Angelika Schierhorn & Per Westermark & Gunilla T. Westermark & Bouke P. C. Hazenberg & Nikolaus Grigorieff & Marcus Fändrich & Matthias Schmidt, 2019. "Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09033-z
    DOI: 10.1038/s41467-019-09033-z
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    Cited by:

    1. Kartikay Sharma & Fabian Stockert & Jayakrishna Shenoy & Mélanie Berbon & Muhammed Bilal Abdul-Shukkoor & Birgit Habenstein & Antoine Loquet & Matthias Schmidt & Marcus Fändrich, 2024. "Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    2. Binh An Nguyen & Virender Singh & Shumaila Afrin & Anna Yakubovska & Lanie Wang & Yasmin Ahmed & Rose Pedretti & Maria del Carmen Fernandez-Ramirez & Preeti Singh & Maja Pękała & Luis O. Cabrera Herna, 2024. "Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Irina Iakovleva & Michael Hall & Melanie Oelker & Linda Sandblad & Intissar Anan & A. Elisabeth Sauer-Eriksson, 2021. "Structural basis for transthyretin amyloid formation in vitreous body of the eye," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Maximilian Steinebrei & Julian Baur & Anaviggha Pradhan & Niklas Kupfer & Sebastian Wiese & Ute Hegenbart & Stefan O. Schönland & Matthias Schmidt & Marcus Fändrich, 2023. "Common transthyretin-derived amyloid fibril structures in patients with hereditary ATTR amyloidosis," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    5. Sara Karimi-Farsijani & Peter Benedikt Pfeiffer & Sambhasan Banerjee & Julian Baur & Lukas Kuhn & Niklas Kupfer & Ute Hegenbart & Stefan O. Schönland & Sebastian Wiese & Christian Haupt & Matthias Sch, 2024. "Light chain mutations contribute to defining the fibril morphology in systemic AL amyloidosis," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    6. Nikolaos Louros & Meine Ramakers & Emiel Michiels & Katerina Konstantoulea & Chiara Morelli & Teresa Garcia & Nele Moonen & Sam D’Haeyer & Vera Goossens & Dietmar Rudolf Thal & Dominique Audenaert & F, 2022. "Mapping the sequence specificity of heterotypic amyloid interactions enables the identification of aggregation modifiers," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    7. Tim Schulte & Antonio Chaves-Sanjuan & Giulia Mazzini & Valentina Speranzini & Francesca Lavatelli & Filippo Ferri & Carlo Palizzotto & Maria Mazza & Paolo Milani & Mario Nuvolone & Anne-Cathrine Vogt, 2022. "Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    8. Stephen J. Klawa & Michelle Lee & Kyle D. Riker & Tengyue Jian & Qunzhao Wang & Yuan Gao & Margaret L. Daly & Shreeya Bhonge & W. Seth Childers & Tolulope O. Omosun & Anil K. Mehta & David G. Lynn & R, 2024. "Uncovering supramolecular chirality codes for the design of tunable biomaterials," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. 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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