+Open data
-Basic information
Entry | Database: PDB / ID: 8efu | ||||||
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Title | a22L prion fibril | ||||||
Components | Major prion protein | ||||||
Keywords | PROTEIN FIBRIL / Prion / Fibril / GPI-anchorless / PrP / Infectious / Amyloid / Brain-derived / ex vivo / Prion strain | ||||||
Function / homology | Function and homology information Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / negative regulation of amyloid precursor protein catabolic process / lamin binding / regulation of glutamate receptor signaling pathway / regulation of calcium ion import across plasma membrane / aspartic-type endopeptidase inhibitor activity / glycosaminoglycan binding / ATP-dependent protein binding / regulation of potassium ion transmembrane transport / negative regulation of interleukin-17 production ...Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / negative regulation of amyloid precursor protein catabolic process / lamin binding / regulation of glutamate receptor signaling pathway / regulation of calcium ion import across plasma membrane / aspartic-type endopeptidase inhibitor activity / glycosaminoglycan binding / ATP-dependent protein binding / regulation of potassium ion transmembrane transport / negative regulation of interleukin-17 production / negative regulation of dendritic spine maintenance / type 5 metabotropic glutamate receptor binding / cupric ion binding / nucleobase-containing compound metabolic process / response to copper ion / negative regulation of calcineurin-NFAT signaling cascade / negative regulation of interleukin-2 production / negative regulation of T cell receptor signaling pathway / activation of protein kinase activity / cuprous ion binding / negative regulation of amyloid-beta formation / negative regulation of activated T cell proliferation / response to amyloid-beta / : / negative regulation of type II interferon production / negative regulation of long-term synaptic potentiation / intracellular copper ion homeostasis / positive regulation of protein targeting to membrane / side of membrane / response to cadmium ion / regulation of peptidyl-tyrosine phosphorylation / inclusion body / cellular response to copper ion / neuron projection maintenance / negative regulation of protein phosphorylation / molecular condensate scaffold activity / molecular function activator activity / positive regulation of protein localization to plasma membrane / protein destabilization / protein homooligomerization / negative regulation of DNA-binding transcription factor activity / terminal bouton / cellular response to amyloid-beta / regulation of protein localization / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of neuron apoptotic process / cellular response to xenobiotic stimulus / signaling receptor activity / amyloid-beta binding / protein-folding chaperone binding / microtubule binding / nuclear membrane / protease binding / response to oxidative stress / transmembrane transporter binding / molecular adaptor activity / postsynaptic density / learning or memory / membrane raft / copper ion binding / dendrite / protein-containing complex binding / negative regulation of apoptotic process / Golgi apparatus / cell surface / endoplasmic reticulum / identical protein binding / membrane / metal ion binding / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Hoyt, F. / Caughey, B. | ||||||
Funding support | United States, 1items
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Citation | Journal: PLoS Pathog / Year: 2022 Title: Cryo-EM of prion strains from the same genotype of host identifies conformational determinants. Authors: Forrest Hoyt / Parvez Alam / Efrosini Artikis / Cindi L Schwartz / Andrew G Hughson / Brent Race / Chase Baune / Gregory J Raymond / Gerald S Baron / Allison Kraus / Byron Caughey / Abstract: Prion strains in a given type of mammalian host are distinguished by differences in clinical presentation, neuropathological lesions, survival time, and characteristics of the infecting prion protein ...Prion strains in a given type of mammalian host are distinguished by differences in clinical presentation, neuropathological lesions, survival time, and characteristics of the infecting prion protein (PrP) assemblies. Near-atomic structures of prions from two host species with different PrP sequences have been determined but comparisons of distinct prion strains of the same amino acid sequence are needed to identify purely conformational determinants of prion strain characteristics. Here we report a 3.2 Å resolution cryogenic electron microscopy-based structure of the 22L prion strain purified from the brains of mice engineered to express only PrP lacking glycophosphatidylinositol anchors [anchorless (a) 22L]. Comparison of this near-atomic structure to our recently determined structure of the aRML strain propagated in the same inbred mouse reveals that these two mouse prion strains have distinct conformational templates for growth via incorporation of PrP molecules of the same sequence. Both a22L and aRML are assembled as stacks of PrP molecules forming parallel in-register intermolecular β-sheets and intervening loops, with single monomers spanning the ordered fibril core. Each monomer shares an N-terminal steric zipper, three major arches, and an overall V-shape, but the details of these and other conformational features differ markedly. Thus, variations in shared conformational motifs within a parallel in-register β-stack fibril architecture provide a structural basis for prion strain differentiation within a single host genotype. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8efu.cif.gz | 141 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8efu.ent.gz | 112.5 KB | Display | PDB format |
PDBx/mmJSON format | 8efu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8efu_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8efu_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8efu_validation.xml.gz | 36.7 KB | Display | |
Data in CIF | 8efu_validation.cif.gz | 52.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ef/8efu ftp://data.pdbj.org/pub/pdb/validation_reports/ef/8efu | HTTPS FTP |
-Related structure data
Related structure data | 28089MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 25550.348 Da / Num. of mol.: 5 / Mutation: S233Stop / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: P04925 |
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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: GPI anchorless underglycosylated 22L prion fibril / Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Mus musculus (house mouse) / Organ: Brain |
Buffer solution | pH: 7.4 Details: Sample suspended in 20 mM Tris pH 7.4, 100 mM containing 0.02% amphipol 8-35 |
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: C-flat-1.2/1.3 |
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: 81000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 500 nm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 57 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of real images: 4449 |
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: -0.565 ° / Axial rise/subunit: 4.75 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 226306 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 16409 Details: Pixel size was corrected in post processing from 1.1 A/pix to 1.045 A/pix to correct an error in the reported magnification pixel size. Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |