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.

Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter / T. Schulte, A. Chaves-Sanjuan, G. Mazzini, V. Speranzini, F. Lavatelli, F. Ferri, C. Palizzotto, M. Mazza, P. Milani, M. Nuvolone, A. Vogt, M. Vogel, G. Palladini, G. Merlini, M. Bolognesi, S. Ferro, E. Zini, S. Ricagno. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 13:1(2022), pp. 7041.1-7041.9. [10.1038/s41467-022-34743-2]

Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter

A. Chaves-Sanjuan
Secondo
;
V. Speranzini;M. Mazza;M. Bolognesi;S. Ricagno
Ultimo
2022

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 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.
Settore BIO/10 - Biochimica
PRIN202022SRICA_01 - Protein misfolding in AL amyloidosis: from fibrillar deposits to soluble toxicity - RICAGNO, STEFANO - PRIN2020 - PRIN bando 2020 - 2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/945950
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