+Open data
-Basic information
Entry | Database: PDB / ID: 9dmz | ||||||
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Title | Glycosylated chronic wasting disease prion fibril | ||||||
Components | Major prion protein | ||||||
Keywords | PROTEIN FIBRIL / Prion / Chronic Wasting Disease / Deer / Fibril / GPI-anchor / Glycosylation / PrP / Infectious / Amyloid / Brain-derived / ex vivo / Prion strain | ||||||
Function / homology | Function and homology information side of membrane / protein homooligomerization / Golgi apparatus / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Odocoileus virginianus (white-tailed deer) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
Authors | Caughey, B. / Hoyt, F. / Alam, P. / Artikis, E. / Soukup, J. / Hughson, A. / Schwartz, C. / Race, B. / Barbian, K. | ||||||
Funding support | United States, 1items
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Citation | Journal: Acta Neuropathol / Year: 2024 Title: Cryo-EM structure of a natural prion: chronic wasting disease fibrils from deer. Authors: Parvez Alam / Forrest Hoyt / Efrosini Artikis / Jakub Soukup / Andrew G Hughson / Cindi L Schwartz / Kent Barbian / Michael W Miller / Brent Race / Byron Caughey / Abstract: Chronic wasting disease (CWD) is a widely distributed prion disease of cervids with implications for wildlife conservation and also for human and livestock health. The structures of infectious prions ...Chronic wasting disease (CWD) is a widely distributed prion disease of cervids with implications for wildlife conservation and also for human and livestock health. The structures of infectious prions that cause CWD and other natural prion diseases of mammalian hosts have been poorly understood. Here we report a 2.8 Å resolution cryogenic electron microscopy-based structure of CWD prion fibrils from the brain of a naturally infected white-tailed deer expressing the most common wild-type PrP sequence. Like recently solved rodent-adapted scrapie prion fibrils, our atomic model of CWD fibrils contains single stacks of PrP molecules forming parallel in-register intermolecular β-sheets and intervening loops comprising major N- and C-terminal lobes within the fibril cross-section. However, CWD fibrils from a natural cervid host differ markedly from the rodent structures in many other features, including a ~ 180° twist in the relative orientation of the lobes. This CWD structure suggests mechanisms underlying the apparent CWD transmission barrier to humans and should facilitate more rational approaches to the development of CWD vaccines and therapeutics. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9dmz.cif.gz | 153.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb9dmz.ent.gz | 118.3 KB | Display | PDB format |
PDBx/mmJSON format | 9dmz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9dmz_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 9dmz_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 9dmz_validation.xml.gz | 42.6 KB | Display | |
Data in CIF | 9dmz_validation.cif.gz | 55.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dm/9dmz ftp://data.pdbj.org/pub/pdb/validation_reports/dm/9dmz | HTTPS FTP |
-Related structure data
Related structure data | 47021MC 9dmyC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Symmetry | Helical symmetry: (Circular symmetry: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 5 / Rise per n subunits: 4.779 Å / Rotation per n subunits: -0.2913 °) |
-Components
#1: Protein | Mass: 27965.486 Da / Num. of mol.: 5 / Source method: isolated from a natural source Source: (natural) Odocoileus virginianus (white-tailed deer) References: UniProt: Q7JIQ1 #2: Sugar | ChemComp-NAG / Has ligand of interest | N | Has protein modification | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: Naturally occurring chronic wasting disease prion fibril Type: COMPLEX / Entity ID: #1 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Odocoileus virginianus (white-tailed deer) / Organ: Brain |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 295 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -0.2913 ° / Axial rise/subunit: 4.779 Å / Axial symmetry: C1 | |||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 535858 | |||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 7346 / Symmetry type: HELICAL | |||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | |||||||||||||||||||||||||||||||||||
Refine LS restraints |
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