Schulte, Tim; Chaves-Sanjuan, Antonio; Mazzini, Giulia; Speranzini, Valentina; Lavatelli, Francesca; Ferri, Filippo; Palizzotto, Carlo; Mazza, Maria; Milani, Paolo; Nuvolone, Mario; Vogt, Anne-Cathrine; Vogel, Monique; Palladini, Giovanni; Merlini, Giampaolo; Bolognesi, Martino; Ferro, Silvia; Zini, Eric; Ricagno, Stefano (2022). Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter. Nature communications, 13(1), p. 7041. Nature Publishing Group 10.1038/s41467-022-34743-2
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology |
UniBE Contributor: |
Vogt, Anne-Cathrine Sarah, Vogel, Monique |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
22 Nov 2022 10:48 |
Last Modified: |
05 Dec 2022 16:28 |
Publisher DOI: |
10.1038/s41467-022-34743-2 |
PubMed ID: |
36396658 |
BORIS DOI: |
10.48350/174932 |
URI: |
https://boris.unibe.ch/id/eprint/174932 |
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