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

Liberta, F., Loerch, S., Rennegarbege, M., Schierhorn, A., Westermark, P., Westermark, G. T., Hazenberg, B. P. C., Grigorieff, N., Faendrich, M. & Schmidt, M., 7-Mar-2019, In : Nature Communications. 10, 10 p., 1104.

Research output: Contribution to journalArticleAcademicpeer-review

  • Falk Liberta
  • Sarah Loerch
  • Matthies Rennegarbege
  • Angelika Schierhorn
  • Per Westermark
  • Gunilla T. Westermark
  • Bouke P. C. Hazenberg
  • Nikolaus Grigorieff
  • Marcus Faendrich
  • Matthias Schmidt

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 angstrom and 2.7 angstrom 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-beta sheets and overall fold of the fibril proteins. Yet, both proteins adopt highly similar beta-arch conformations within the N-terminal similar to 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.

Original languageEnglish
Article number1104
Number of pages10
JournalNature Communications
Volume10
Publication statusPublished - 7-Mar-2019

    Keywords

  • SECONDARY STRUCTURE, PROTEIN, PATHOGENESIS, VISUALIZATION, TRANSMISSION, POLYMORPHISM, VALIDATION, DISEASE, MODEL

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