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Publication Abstract from PubMed

AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-beta 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 A 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-beta 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.

Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter.,Schulte T, Chaves-Sanjuan A, Mazzini G, Speranzini V, Lavatelli F, Ferri F, Palizzotto C, Mazza M, Milani P, Nuvolone M, Vogt AC, Vogel M, Palladini G, Merlini G, Bolognesi M, Ferro S, Zini E, Ricagno S Nat Commun. 2022 Nov 17;13(1):7041. doi: 10.1038/s41467-022-34743-2. PMID:36396658^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.