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Open data
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Basic information
Entry | Database: PDB / ID: 7lna | |||||||||
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Title | Infectious mammalian prion fibril (263K scrapie) | |||||||||
![]() | Major prion protein | |||||||||
![]() | PROTEIN FIBRIL / infectious mammalian prion / templating / glycosylated glycophophatidlyinositol-anchored amyloid / PIRIBS | |||||||||
Function / homology | ![]() regulation of glutamate receptor signaling pathway / regulation of calcium ion import across plasma membrane / aspartic-type endopeptidase inhibitor activity / glycosaminoglycan 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 / negative regulation of calcineurin-NFAT signaling cascade ...regulation of glutamate receptor signaling pathway / regulation of calcium ion import across plasma membrane / aspartic-type endopeptidase inhibitor activity / glycosaminoglycan 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 / negative regulation of calcineurin-NFAT signaling cascade / negative regulation of T cell receptor signaling pathway / negative regulation of interleukin-2 production / cuprous ion binding / negative regulation of amyloid-beta formation / negative regulation of activated T cell proliferation / negative regulation of type II interferon production / positive regulation of protein targeting to membrane / side of membrane / inclusion body / cellular response to copper ion / neuron projection maintenance / positive regulation of protein localization to plasma membrane / molecular condensate scaffold activity / negative regulation of protein phosphorylation / molecular function activator activity / protein destabilization / protein homooligomerization / terminal bouton / cellular response to xenobiotic stimulus / cellular response to amyloid-beta / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of neuron apoptotic process / presynapse / signaling receptor activity / amyloid-beta binding / nuclear membrane / microtubule binding / protease binding / response to oxidative stress / amyloid fibril formation / learning or memory / regulation of cell cycle / membrane raft / copper ion binding / dendrite / negative regulation of apoptotic process / protein-containing complex binding / cell surface / Golgi apparatus / endoplasmic reticulum / identical protein binding / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.14 Å | |||||||||
![]() | Kraus, A. / Hoyt, F. / Schwartz, C.L. / Hansen, B. / Hughson, A.G. / Artikis, E. / Race, B. / Caughey, B. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: High-resolution structure and strain comparison of infectious mammalian prions. Authors: Allison Kraus / Forrest Hoyt / Cindi L Schwartz / Bryan Hansen / Efrosini Artikis / Andrew G Hughson / Gregory J Raymond / Brent Race / Gerald S Baron / Byron Caughey / ![]() Abstract: Within the extensive range of self-propagating pathologic protein aggregates of mammals, prions are the most clearly infectious (e.g., ∼10 lethal doses per milligram). The structures of such lethal ...Within the extensive range of self-propagating pathologic protein aggregates of mammals, prions are the most clearly infectious (e.g., ∼10 lethal doses per milligram). The structures of such lethal assemblies of PrP molecules have been poorly understood. Here we report a near-atomic core structure of a brain-derived, fully infectious prion (263K strain). Cryo-electron microscopy showed amyloid fibrils assembled with parallel in-register intermolecular β sheets. Each monomer provides one rung of the ordered fibril core, with N-linked glycans and glycolipid anchors projecting outward. Thus, single monomers form the templating surface for incoming monomers at fibril ends, where prion growth occurs. Comparison to another prion strain (aRML) revealed major differences in fibril morphology but, like 263K, an asymmetric fibril cross-section without paired protofilaments. These findings provide structural insights into prion propagation, strains, species barriers, and membrane pathogenesis. This structure also helps frame considerations of factors influencing the relative transmissibility of other pathologic amyloids. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 76.8 KB | Display | ![]() |
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PDB format | ![]() | 57.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 23459MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
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Components
#1: Protein | Mass: 16264.101 Da / Num. of mol.: 3 / Source method: isolated from a natural source Details: Protease-resistant glycosylated, glycophophatidlyinositol-anchored infectious prion amyloid core (inclusive of residues 90-231). Source: (natural) ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: infectious mammalian prion fibril (263K scrapie) / Type: COMPLEX Details: Purified from brains of hamsters with clinical scrapie prion disease. Entity ID: all / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: Solarus 950 (Gatan, Pleasanton CA) / 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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: REFMAC / Version: 5.8.0258 / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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Image processing | Details: Processing and reconstruction was conducted in Relion as per Scheres, Acta Cryst. (2020). D76, 94-101 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 337368 Details: Filament start and end positions were picked manually in RELION. Particles were extracted with an interbox distance of 14.7A along the filament axis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.14 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 15884 / Algorithm: FOURIER SPACE Details: Auto-refinement was then performed while optimizing the helical twist and rise. Auto-refinement with refinement of twist and rise yielded a final map with a twist of -0.847 degree and rise ...Details: Auto-refinement was then performed while optimizing the helical twist and rise. Auto-refinement with refinement of twist and rise yielded a final map with a twist of -0.847 degree and rise of 4.874 angstrom. Iterative cycles of CTF refinement, Bayesian polishing, and auto refinement were used until resolution estimates stabilized. Post processing in RELION was performed with a soft-edged mask representing 10% of the central Z length of the fibril. Sharpening was applied with a B-factor of -31 square angstrom. Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: RECIPROCAL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 3.1→114.45 Å / Cor.coef. Fo:Fc: 0.808 / ESU R: 0.544 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES
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Solvent computation | Solvent model: PARAMETERS FOR MASK CACLULATION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 39.924 Å2
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Refinement step | Cycle: 1 / Total: 3171 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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