+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16952 | ||||||||||||||||||
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Title | Murine type II Abeta fibril from tgAPPSwe mouse | ||||||||||||||||||
Map data | Ex vivo Abeta fibril from tg-APPSwe mouse brain. | ||||||||||||||||||
Sample |
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Keywords | Amyloid fibril / PROTEIN FIBRIL | ||||||||||||||||||
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 / microglial cell activation / regulation of long-term neuronal synaptic plasticity / positive regulation of JNK cascade / 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 | Homo sapiens (human) | ||||||||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.8 Å | ||||||||||||||||||
Authors | Zielinski M / Peralta Reyes FS / Gremer L / Schemmert S / Frieg B / Willuweit A / Donner L / Elvers M / Nilsson LNG / Syvanen S ...Zielinski M / Peralta Reyes FS / Gremer L / Schemmert S / Frieg B / Willuweit A / Donner L / Elvers M / Nilsson LNG / Syvanen S / Sehlin D / Ingelsson M / Willbold D / Schroeder GF | ||||||||||||||||||
Funding support | Germany, Sweden, 5 items
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Citation | Journal: Nat Neurosci / Year: 2023 Title: Cryo-EM of Aβ fibrils from mouse models find tg-APP fibrils resemble those found in patients with sporadic Alzheimer's disease. Authors: Mara Zielinski / Fernanda S Peralta Reyes / Lothar Gremer / Sarah Schemmert / Benedikt Frieg / Luisa U Schäfer / Antje Willuweit / Lili Donner / Margitta Elvers / Lars N G Nilsson / Stina ...Authors: Mara Zielinski / Fernanda S Peralta Reyes / Lothar Gremer / Sarah Schemmert / Benedikt Frieg / Luisa U Schäfer / Antje Willuweit / Lili Donner / Margitta Elvers / Lars N G Nilsson / Stina Syvänen / Dag Sehlin / Martin Ingelsson / Dieter Willbold / Gunnar F Schröder / Abstract: The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties ...The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer's disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 and tg-SwDI models, whereas the human type II filament fold was found in the ARTE10, tg-APP and APP23 models. The tg-APP mice showed an Aβ fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer's disease. A detailed assessment of the Aβ fibril structure is key to the selection of adequate mouse models for the preclinical development of novel plaque-targeting therapeutics and positron emission tomography imaging tracers in Alzheimer's disease. | ||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16952.map.gz | 28.4 MB | EMDB map data format | |
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Header (meta data) | emd-16952-v30.xml emd-16952.xml | 15.7 KB 15.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16952_fsc.xml | 9.6 KB | Display | FSC data file |
Images | emd_16952.png | 44.8 KB | ||
Filedesc metadata | emd-16952.cif.gz | 5.3 KB | ||
Others | emd_16952_half_map_1.map.gz emd_16952_half_map_2.map.gz | 57.1 MB 57.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16952 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16952 | HTTPS FTP |
-Related structure data
Related structure data | 8ol6MC 8ol2C 8ol3C 8ol5C 8ol7C 8olgC 8olnC 8oloC 8olqC 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_16952.map.gz / Format: CCP4 / Size: 75.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Ex vivo Abeta fibril from tg-APPSwe mouse brain. | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.808 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Ex vivo Abeta fibril from tg-APPSwe mouse brain. Half map 1.
File | emd_16952_half_map_1.map | ||||||||||||
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Annotation | Ex vivo Abeta fibril from tg-APPSwe mouse brain. Half map 1. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Ex vivo Abeta fibril from tg-APPSwe mouse brain. Half map 2.
File | emd_16952_half_map_2.map | ||||||||||||
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Annotation | Ex vivo Abeta fibril from tg-APPSwe mouse brain. Half map 2. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Amyloid fibril of amyloid-beta
Entire | Name: Amyloid fibril of amyloid-beta |
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Components |
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-Supramolecule #1: Amyloid fibril of amyloid-beta
Supramolecule | Name: Amyloid fibril of amyloid-beta / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 20 kDa/nm |
-Macromolecule #1: Amyloid-beta protein 42
Macromolecule | Name: Amyloid-beta protein 42 / type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) / Organ: Brain |
Molecular weight | Theoretical: 4.520087 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IA UniProtKB: Amyloid-beta precursor protein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 9370 / Average electron dose: 40.35 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |