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TitleCryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 7041, Year 2022
Publish dateNov 17, 2022
AuthorsTim 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 AbstractAA 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 linksNat Commun / PubMed:36396658 / PubMed Central
MethodsEM (helical sym.)
Resolution3.3 Å
Structure data

14726

7zh7

EMDB-14726, PDB-7zh7:
Cryo-EM structure of ex vivo AA amyloid from renal tissue of a short hair cat deceased in a shelter
Method: EM (helical sym.) / Resolution: 3.3 Å

Source
  • felis catus (domestic cat)
  • domestic cat (domestic cat)
KeywordsPROTEIN FIBRIL / AA amyloidosis / cat / Serum amyloid A

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