+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23459 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Infectious mammalian prion fibril (263K scrapie) | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Function / homology | Function and homology information 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 interleukin-2 production / negative regulation of T cell receptor signaling pathway / 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 / 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 / terminal bouton / cellular response to amyloid-beta / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of neuron apoptotic process / cellular response to xenobiotic stimulus / signaling receptor activity / amyloid-beta binding / microtubule binding / protease binding / nuclear membrane / response to oxidative stress / amyloid fibril formation / cell cycle / learning or memory / regulation of cell cycle / membrane raft / copper ion binding / dendrite / protein-containing complex binding / negative regulation of apoptotic process / Golgi apparatus / cell surface / endoplasmic reticulum / identical protein binding / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Mesocricetus auratus (golden hamster) / Golden hamster (golden hamster) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.14 Å | |||||||||
Authors | Kraus A / Hoyt F / Schwartz CL / Hansen B / Hughson AG / Artikis E / Race B / Caughey B | |||||||||
Funding support | United States, 2 items
| |||||||||
Citation | Journal: Mol Cell / Year: 2021 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23459.map.gz | 7.4 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-23459-v30.xml emd-23459.xml | 17.7 KB 17.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_23459_fsc.xml | 12 KB | Display | FSC data file |
Images | emd_23459.png | 48.7 KB | ||
Others | emd_23459_half_map_1.map.gz emd_23459_half_map_2.map.gz | 118.4 MB 118.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23459 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23459 | HTTPS FTP |
-Validation report
Summary document | emd_23459_validation.pdf.gz | 707.9 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_23459_full_validation.pdf.gz | 707.4 KB | Display | |
Data in XML | emd_23459_validation.xml.gz | 19.4 KB | Display | |
Data in CIF | emd_23459_validation.cif.gz | 25.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23459 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23459 | HTTPS FTP |
-Related structure data
Related structure data | 7lnaMC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_23459.map.gz / Format: CCP4 / Size: 149.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.09 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Half map: #2
File | emd_23459_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_23459_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : infectious mammalian prion fibril (263K scrapie)
Entire | Name: infectious mammalian prion fibril (263K scrapie) |
---|---|
Components |
|
-Supramolecule #1: infectious mammalian prion fibril (263K scrapie)
Supramolecule | Name: infectious mammalian prion fibril (263K scrapie) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Purified from brains of hamsters with clinical scrapie prion disease. |
---|---|
Source (natural) | Organism: Mesocricetus auratus (golden hamster) / Organ: brain / Tissue: brain |
-Macromolecule #1: Major prion protein
Macromolecule | Name: Major prion protein / type: protein_or_peptide / ID: 1 Details: Protease-resistant glycosylated, glycophophatidlyinositol-anchored infectious prion amyloid core (inclusive of residues 90-231). Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Golden hamster (golden hamster) / Organ: brain |
Molecular weight | Theoretical: 16.264101 KDa |
Sequence | String: GQGGGTHNQW NKPSKPKTNM KHMAGAAAAG AVVGGLGGYM LGSAMSRPMM HFGNDWEDRY YRENMNRYPN QVYYRPVDQY NNQNNFVHD CVNITIKQHT VTTTTKGENF TETDIKIMER VVEQMCTTQY QKESQAYYDG RRS |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Atmosphere: OTHER / Pretreatment - Pressure: 0.07200000000000001 kPa / Details: Solarus 950 (Gatan, Pleasanton CA) |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 295 K / Instrument: LEICA EM GP |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: AB INITIO MODEL |
---|---|
Output model | PDB-7lna: |