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bioRxiv · 10.1101/2022.05.09.491126

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, A.-C.·Palladini, G.·Merlini, G.·Bolognesi, M.·Ferro, S.·Zini, E.·Ricagno, S.
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Abstract

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. The disease can be transmitted horizontally, likely facilitated by prion-like mechanism, in captive animals leading to extreme disease prevalence, e.g. 70% in captive cheetah and 57-73% in domestic short hair (DSH) cats kept in shelters. Herein, we present the 3.3 [A] cryo-EM structure of an AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure. 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. Based on shared disease profiles and almost identical protein sequences, we propose a similar amyloid fold of deposits identified previously in captive cheetah.

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Schulte, T., Chaves-Sanjuan, A., Mazzini, G., Speranzini, V., Lavatelli, F., Ferri, F., Palizzotto, C., Mazza, M., Milani, P., Nuvolone, M., Vogt, A.-C., Palladini, G., Merlini, G., Bolognesi, M., Ferro, S., Zini, E., Ricagno, S.. 2022-05-09. Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter. https://doi.org/10.1101/2022.05.09.491126

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