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Title | Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 7041, Year 2022 |
Publish date | Nov 17, 2022 |
Authors | Tim Schulte / Antonio Chaves-Sanjuan / Giulia Mazzini / Valentina Speranzini / Francesca Lavatelli / Filippo Ferri / Carlo Palizzotto / Maria Mazza / Paolo Milani / Mario Nuvolone / Anne-Cathrine Vogt / Monique Vogel / Giovanni Palladini / Giampaolo Merlini / Martino Bolognesi / Silvia Ferro / Eric Zini / Stefano Ricagno / |
PubMed Abstract | AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-β amyloid in multiple organs in humans and animals. AA amyloidosis occurs at ...AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-β amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during chronic inflammation. Prion-like transmission was reported as possible cause of extreme AA amyloidosis prevalence in captive animals, e.g. 70% in cheetah and 57-73% in domestic short hair (DSH) cats kept in zoos and shelters, respectively. Herein, we present the 3.3 Å cryo-EM structure of AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure, deceased in a shelter with extreme disease prevalence. The structure reveals a cross-β architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a distinct amyloid fold. Inclusion of an eight-residue insert unique to feline SAA contributes to increased amyloid stability. The presented feline AA amyloid structure is fully compatible with the 99% identical amino acid sequence of amyloid fragments of captive cheetah. |
External links | Nat Commun / PubMed:36396658 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 3.3 Å |
Structure data | EMDB-14726, PDB-7zh7: |
Source |
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Keywords | PROTEIN FIBRIL / AA amyloidosis / cat / Serum amyloid A |