- PDB-7zh7: Cryo-EM structure of ex vivo AA amyloid from renal tissue of a sh... -
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Basic information
Entry
Database: PDB / ID: 7zh7
Title
Cryo-EM structure of ex vivo AA amyloid from renal tissue of a short hair cat deceased in a shelter
Components
Serum amyloid A protein
Keywords
PROTEIN FIBRIL / AA amyloidosis / cat / Serum amyloid A
Function / homology
Serum amyloid A protein / Serum amyloid A protein / Serum amyloid A proteins signature. / Serum amyloid A proteins / high-density lipoprotein particle / acute-phase response / Serum amyloid A protein
Function and homology information
Biological species
Felis catus (domestic cat)
Method
ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.3 Å
Journal: Nat Commun / Year: 2022 Title: Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter. Authors: Tim Schulte / Antonio Chaves-Sanjuan / Giulia Mazzini / Valentina Speranzini / Francesca Lavatelli / Filippo Ferri / Carlo Palizzotto / Maria Mazza / Paolo Milani / Mario Nuvolone / Anne- ...Authors: Tim Schulte / Antonio Chaves-Sanjuan / Giulia Mazzini / Valentina Speranzini / Francesca Lavatelli / Filippo Ferri / Carlo Palizzotto / Maria Mazza / Paolo Milani / Mario Nuvolone / Anne-Cathrine Vogt / Monique Vogel / Giovanni Palladini / Giampaolo Merlini / Martino Bolognesi / Silvia Ferro / Eric Zini / Stefano Ricagno / 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 ...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.
A: Serum amyloid A protein B: Serum amyloid A protein C: Serum amyloid A protein D: Serum amyloid A protein E: Serum amyloid A protein F: Serum amyloid A protein G: Serum amyloid A protein H: Serum amyloid A protein I: Serum amyloid A protein J: Serum amyloid A protein
Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen support
Details: glow discharged for 30s at 30mA using a GloQube system Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: C-flat-1.2/1.3
Vitrification
Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 %
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Electron microscopy imaging
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
Microscopy
Model: FEI TALOS ARCTICA
Electron gun
Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lens
Mode: BRIGHT FIELD / Nominal magnification: 120000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 600 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE
Specimen holder
Cryogen: NITROGEN
Image recording
Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2652 / Details: images takes for analysis
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