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

Autor: Schulte T; Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato, 20097, Milan, Italy., Chaves-Sanjuan A; Department of Biosciences, Università degli Studi di Milano, Milan, Italy.; Pediatric Research Center Fondazione R.E. Invernizzi and NOLIMITS Center, Università degli Studi di Milano, Milan, Italy., Mazzini G; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Speranzini V; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Lavatelli F; Department of Molecular Medicine, University of Pavia, Pavia, Italy., Ferri F; AniCura Istituto Veterinario Novara, Strada Provinciale 9, 28060, Granozzo con Monticello, Novara, Italy., Palizzotto C; AniCura Istituto Veterinario Novara, Strada Provinciale 9, 28060, Granozzo con Monticello, Novara, Italy., Mazza M; Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d'Aosta, S.C. Diagnostica Specialistica, Via Bologna 148, 10154, Torino, Italy., Milani P; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Nuvolone M; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Vogt AC; Department for BioMedical Research (DBMR), University of Bern, 3008, Bern, Switzerland.; Department of Rheumatology and Immunology, University Hospital Bern, 3010, Bern, Switzerland., Vogel M; Department for BioMedical Research (DBMR), University of Bern, 3008, Bern, Switzerland.; Department of Rheumatology and Immunology, University Hospital Bern, 3010, Bern, Switzerland., Palladini G; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Merlini G; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Bolognesi M; Department of Biosciences, Università degli Studi di Milano, Milan, Italy.; Pediatric Research Center Fondazione R.E. Invernizzi and NOLIMITS Center, Università degli Studi di Milano, Milan, Italy., Ferro S; Department of Comparative Biomedicine and Food Sciences, University of Padova, viale dell'Università 16, 35020, Legnaro, Padua, Italy., Zini E; AniCura Istituto Veterinario Novara, Strada Provinciale 9, 28060, Granozzo con Monticello, Novara, Italy.; Department of Animal Medicine, Production and Health, University of Padua, viale dell'Università 16, 35020, Legnaro, Padua, Italy.; Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland., Ricagno S; Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato, 20097, Milan, Italy. stefano.ricagno@unimi.it.; Department of Biosciences, Università degli Studi di Milano, Milan, Italy. stefano.ricagno@unimi.it.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 17; Vol. 13 (1), pp. 7041. Date of Electronic Publication: 2022 Nov 17.
DOI: 10.1038/s41467-022-34743-2
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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