+
Open data
-
Basic information
Entry | ![]() | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Murine type III Abeta fibril from ARTE10 mouse | ||||||||||||||||||
![]() | Ex vivo Abeta40 fibril from ARTE10 mouse brain. | ||||||||||||||||||
![]() |
| ||||||||||||||||||
![]() | Amyloid fibril / PROTEIN FIBRIL | ||||||||||||||||||
Function / homology | ![]() regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity ...regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / NMDA selective glutamate receptor signaling pathway / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / suckling behavior / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / The NLRP3 inflammasome / regulation of presynapse assembly / transition metal ion binding / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / negative regulation of neuron differentiation / ECM proteoglycans / intracellular copper ion homeostasis / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / protein serine/threonine kinase binding / positive regulation of chemokine production / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / forebrain development / Notch signaling pathway / Mitochondrial protein degradation / neuron projection maintenance / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / response to interleukin-1 / cholesterol metabolic process / positive regulation of mitotic cell cycle / extracellular matrix organization / adult locomotory behavior / axonogenesis / platelet alpha granule lumen / trans-Golgi network membrane / positive regulation of peptidyl-threonine phosphorylation / positive regulation of interleukin-1 beta production / learning / dendritic shaft / positive regulation of long-term synaptic potentiation / central nervous system development / locomotory behavior / endosome lumen / astrocyte activation / positive regulation of JNK cascade / Post-translational protein phosphorylation / synapse organization / microglial cell activation / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / serine-type endopeptidase inhibitor activity / visual learning / neuromuscular junction / recycling endosome / cognition / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of interleukin-6 production / cellular response to amyloid-beta / endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle / Platelet degranulation Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||||||||
![]() | 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 | ![]() ![]()
| ||||||||||||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 92.7 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 15.4 KB 15.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 53.6 KB | ||
Filedesc metadata | ![]() | 5.4 KB | ||
Others | ![]() ![]() | 79.3 MB 79.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8oloMC ![]() 8ol2C ![]() 8ol3C ![]() 8ol5C ![]() 8ol6C ![]() 8ol7C ![]() 8olgC ![]() 8olnC ![]() 8olqC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Ex vivo Abeta40 fibril from ARTE10 mouse brain. | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.808 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Ex vivo Abeta40 fibril from ARTE10 mouse brain. Half map 1.
File | emd_16960_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Ex vivo Abeta40 fibril from ARTE10 mouse brain. Half map 1. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Ex vivo Abeta40 fibril from ARTE10 mouse brain. Half map 2.
File | emd_16960_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Ex vivo Abeta40 fibril from ARTE10 mouse brain. Half map 2. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Amyloid fibril of amyloid-beta
Entire | Name: Amyloid fibril of amyloid-beta |
---|---|
Components |
|
-Supramolecule #1: Amyloid fibril of amyloid-beta
Supramolecule | Name: Amyloid fibril of amyloid-beta / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() |
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 |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 4.520087 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IA UniProtKB: Amyloid-beta precursor protein |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | helical reconstruction |
Aggregation state | filament |
-
Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-
Electron microscopy
Microscope | TFS KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 9521 / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |