12-15 September 2022
Europe/Rome timezone

Structural Characterization of a post-mortem Amyloid Fibril from a Cat Kidney

13 Sep 2022, 10:45
30m
DCPS Building C11/III Floor/- - Lecture Hall A1 (Università di Trieste)

DCPS Building C11/III Floor/- - Lecture Hall A1

Università di Trieste

50
Keynote Modern Integrative Structural Biology MS

Speaker

Dr Antonio Chaves Sanjuan (Università degli Studi di Milano)

Description

Amyloidosis are systemic diseases characterized by deposition of misfolded proteins into cross-β amyloids in multiple organs in humans and animals. During chronic inflammation, serum amyloid A protein (SAA) levels increases, which result in AA amyloidosis. There is a extreme disease prevalence in captive animals, e.g. 70% in captive cheetah and 57-73% in domestic short hair cats kept in shelters [1], and therefore a prion-like mechanism in amyloid formation has been proposed to explain the horizonal transmission od the disease.
Herein, we present the 3.3 Å resolution cryo-EM structure of fibrils from renal tissue of a cat affected by severe AA amyloidosis in a shelter (Fig. 1) [2]. The fibril is assembled from two twisted proto-filaments, each comprising 76 residues. Amyloid fold and fibril assembly differ from previously reported human and mouse ex vivo AA amyloid structures. Almost identical fibril sequences and similar disease prevalence in related captive cheetah suggest that the structure reported here may depict the prion agent responsible for the high AA amyloidosis prevalence in these two related felids.

Figure 1. Cryo-EM image of a single fibrilwith the reconstructed map and model

[1] F. Ferri, S. Ferro, F. Porporato, C. Callegari, C. Guglielmetti, M. Mazza, M. Ferrero, C. Crinò, E. Gallo, M. Drigo, L.M. Coppola, G. Gerardi, T. Schulte, S. Ricagno, M. Vogel, F. Storni, M.F. Bachmann, A. Vogt, S. Caminito, G. Mazzini, F. Lavatelli, G. Palladini, G. Merlini, E. Zini. BioRxiv 2022.05.04.490646. 2022
[2] T. Schulte, A. Chaves-Sanjuan, G. Mazzini, V. Speranzini, F. Lavatelli, F. Ferri, C. Palizzotto, M. Mazza, P. Milani, M. Nuvolone, A. Vogt, G. Palladini, G. Merlini, M. Bolognesi, S. Ferro, E. Zini, S. Ricagno. bioRxiv 2022.05.09.491126. 2022

Primary author

Dr Antonio Chaves Sanjuan (Università degli Studi di Milano)

Co-authors

Dr Tim Schulte (Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato) Dr Giulia Mazzini (Department of Molecular Medicine, University of Pavia) Dr Valentina Speranzini (Department of Biosciences, Università degli Studi di Milano) Dr Francesca Lavatelli (Department of Molecular Medicine, University of Pavia) Dr Filippo Ferri (AniCura Istituto Veterinario Novara) Dr Carlo Palizzotto (AniCura Istituto Veterinario Novara) Dr Maria Mazza (Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d'Aosta) Dr Paolo Milani (Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo) Dr Mario Nuvolone (Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo) Dr Anne-Cathrine Vogt (Department for BioMedical Research (DBMR), University of Bern) Dr Giovanni Palladini (Department of Molecular Medicine, University of Pavia) Dr Giampaolo Merlini (Department of Molecular Medicine, University of Pavia) Dr Martino Bolognesi (Department of Biosciences, Università degli Studi di Milano) Dr Silvia Ferro (Department of Comparative Biomedicine and Food Sciences, University of Padova) Dr Eric Zini (AniCura Istituto Veterinario Novara) Dr Stefano Ricagno (Department of Biosciences, Università degli Studi di Milano & Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato )

Presentation Materials