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Yorodumi- EMDB-16019: Sarkosyl-extracted AppNL-G-F Abeta42 fibril structure (Methoxy-X0... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16019 | |||||||||
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Title | Sarkosyl-extracted AppNL-G-F Abeta42 fibril structure (Methoxy-X04-labelled mice) | |||||||||
Map data | CryoEM map for extracted AppNLGF Abeta42 fibril after MOX04 labelling | |||||||||
Sample |
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Keywords | Amyloid / fibril / helical / cross-beta / beta amyloid / PROTEIN FIBRIL / ex vivo / arctic mutant / alzheimers disease | |||||||||
Function / homology | Function and homology information regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / smooth endoplasmic reticulum calcium ion homeostasis ...regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / smooth endoplasmic reticulum calcium ion homeostasis / axon midline choice point recognition / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / regulation of Wnt signaling pathway / mating behavior / positive regulation of amyloid fibril formation / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / : / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / presynaptic active zone / nuclear envelope lumen / modulation of excitatory postsynaptic potential / suckling behavior / COPII-coated ER to Golgi transport vesicle / dendrite development / smooth endoplasmic reticulum / regulation of NMDA receptor activity / TRAF6 mediated NF-kB activation / negative regulation of long-term synaptic potentiation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / regulation of presynapse assembly / The NLRP3 inflammasome / intracellular copper ion homeostasis / transition metal ion binding / regulation of multicellular organism growth / negative regulation of neuron differentiation / ECM proteoglycans / spindle midzone / positive regulation of T cell migration / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / forebrain development / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / clathrin-coated pit / Notch signaling pathway / cholesterol metabolic process / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / neuron projection maintenance / positive regulation of glycolytic process / extracellular matrix organization / positive regulation of mitotic cell cycle / response to interleukin-1 / axonogenesis / adult locomotory behavior / trans-Golgi network membrane / dendritic shaft / locomotory behavior / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation / learning / positive regulation of interleukin-1 beta production / central nervous system development / positive regulation of long-term synaptic potentiation / astrocyte activation / endosome lumen / Post-translational protein phosphorylation / synapse organization / positive regulation of JNK cascade / microglial cell activation / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / neuromuscular junction / visual learning / serine-type endopeptidase inhibitor activity / recycling endosome / cognition / positive regulation of inflammatory response / positive regulation of interleukin-6 production / neuron cellular homeostasis / Golgi lumen / endocytosis / positive regulation of non-canonical NF-kappaB signal transduction / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / neuron projection development / cellular response to amyloid-beta / positive regulation of DNA-binding transcription factor activity / G2/M transition of mitotic cell cycle / cell-cell junction / synaptic vesicle / positive regulation of tumor necrosis factor production / regulation of translation Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) / house mouse (house mouse) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Wilkinson M / Leistner C / Burgess A / Goodfellow S / Deuchars S / Ranson NA / Radford SE / Frank RAW | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Nat Commun / Year: 2023 Title: The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain. Authors: Conny Leistner / Martin Wilkinson / Ailidh Burgess / Megan Lovatt / Stanley Goodbody / Yong Xu / Susan Deuchars / Sheena E Radford / Neil A Ranson / René A W Frank / Abstract: Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer's disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. ...Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer's disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. Here, using cryogenic correlated light and electron tomography we report the in situ molecular architecture of Aβ fibrils in the App familial AD mouse model containing the Arctic mutation and an atomic model of ex vivo purified Arctic Aβ fibrils. We show that in-tissue Aβ fibrils are arranged in a lattice or parallel bundles, and are interdigitated by subcellular compartments, extracellular vesicles, extracellular droplets and extracellular multilamellar bodies. The Arctic Aβ fibril differs significantly from an earlier App fibril structure, indicating a striking effect of the Arctic mutation. These structural data also revealed an ensemble of additional fibrillar species, including thin protofilament-like rods and branched fibrils. Together, these results provide a structural model for the dense network architecture that characterises β-amyloid plaque pathology. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16019.map.gz | 5.7 MB | EMDB map data format | |
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Header (meta data) | emd-16019-v30.xml emd-16019.xml | 18.4 KB 18.4 KB | Display Display | EMDB header |
Images | emd_16019.png | 91.5 KB | ||
Others | emd_16019_half_map_1.map.gz emd_16019_half_map_2.map.gz | 56.6 MB 56.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16019 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16019 | HTTPS FTP |
-Related structure data
Related structure data | 8bfbMC 8bfaC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_16019.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | CryoEM map for extracted AppNLGF Abeta42 fibril after MOX04 labelling | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.94 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: halfmap2
File | emd_16019_half_map_1.map | ||||||||||||
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Annotation | halfmap2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: halfmap1
File | emd_16019_half_map_2.map | ||||||||||||
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Annotation | halfmap1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Sarkosyl-extracted AppNL-G-F Abeta42 fibril
Entire | Name: Sarkosyl-extracted AppNL-G-F Abeta42 fibril |
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Components |
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-Supramolecule #1: Sarkosyl-extracted AppNL-G-F Abeta42 fibril
Supramolecule | Name: Sarkosyl-extracted AppNL-G-F Abeta42 fibril / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Fibrils purified from mouse brain labelled with Methoxy-X04 |
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Source (natural) | Organism: Mus musculus (house mouse) / Strain: AppNLGF / Tissue: Brain |
Molecular weight | Theoretical: 4.441 kDa/nm |
-Macromolecule #1: Amyloid-beta precursor protein
Macromolecule | Name: Amyloid-beta precursor protein / type: protein_or_peptide / ID: 1 Details: Humanised Abeta42 from App^NL-G-F mice with arctic mutation (E22G) Number of copies: 10 / Enantiomer: LEVO |
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Source (natural) | Organism: house mouse (house mouse) / Tissue: Brain |
Molecular weight | Theoretical: 4.448025 KDa |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AGDVGSNKGA IIGLMVGGVV IA |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 Component:
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Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 60 sec. | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: 6s blot. | |||||||||
Details | Sarkosyl-insoluble fibrils from App^NL-G-F mouse brain labelled with Methoxy-X04 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.9 µm / Nominal defocus min: 1.4000000000000001 µm / Nominal magnification: 130000 |
Specialist optics | Energy filter - Name: TFS Selectris / Energy filter - Slit width: 10 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 4165 / Average exposure time: 6.0 sec. / Average electron dose: 41.0 e/Å2 Details: 1442 raw EER frames were collected per image and combined into 40 fractions for processing |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Segment selection | Number selected: 136214 / Software - Name: crYOLO Details: Manually picked a subset of images to train a model for automatic fibril segment picking in crYOLO |
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Startup model | Type of model: INSILICO MODEL Details: Model generated from 2D class averages using relion_helix_inimodel2d |
Final angle assignment | Type: NOT APPLICABLE / Software - Name: RELION (ver. 4.0) |
Final reconstruction | Applied symmetry - Helical parameters - Δz: 2.414 Å Applied symmetry - Helical parameters - Δ&Phi: 179.355 ° Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric) Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 4.0) / Number images used: 3640 |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 52 / Target criteria: Correlation coefficient |
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Output model | PDB-8bfb: |