+Open data
-Basic information
Entry | Database: PDB / ID: 8ol5 | ||||||||||||||||||
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Title | Murine type II Abeta fibril from ARTE10 mouse | ||||||||||||||||||
Components | Amyloid-beta protein 42 | ||||||||||||||||||
Keywords | PROTEIN FIBRIL / Amyloid fibril | ||||||||||||||||||
Function / homology | Function and homology information 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 / positive regulation of G2/M transition of mitotic cell cycle / 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 / regulation of peptidyl-tyrosine phosphorylation / 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 / forebrain development / Notch signaling pathway / neuron projection maintenance / positive regulation of protein metabolic process / positive regulation of calcium-mediated signaling / astrocyte activation / 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 / Mitochondrial protein degradation / central nervous system development / locomotory behavior / endosome lumen / 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 / visual learning / neuromuscular junction / positive regulation of non-canonical NF-kappaB signal transduction / recycling endosome / cognition / G2/M transition of mitotic cell cycle / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / 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) / serine-type endopeptidase inhibitor activity / positive regulation of peptidyl-serine phosphorylation / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.4 Å | ||||||||||||||||||
Authors | Zielinski, M. / Peralta Reyes, F.S. / Gremer, L. / Schemmert, S. / Frieg, B. / Willuweit, A. / Donner, L. / Elvers, M. / Nilsson, L.N.G. / Syvanen, S. ...Zielinski, M. / Peralta Reyes, F.S. / Gremer, L. / Schemmert, S. / Frieg, B. / Willuweit, A. / Donner, L. / Elvers, M. / Nilsson, L.N.G. / Syvanen, S. / Sehlin, D. / Ingelsson, M. / Willbold, D. / Schroeder, G.F. | ||||||||||||||||||
Funding support | Germany, Sweden, 5items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ol5.cif.gz | 61.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ol5.ent.gz | 46.4 KB | Display | PDB format |
PDBx/mmJSON format | 8ol5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ol5_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 8ol5_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 8ol5_validation.xml.gz | 25.2 KB | Display | |
Data in CIF | 8ol5_validation.cif.gz | 35.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ol/8ol5 ftp://data.pdbj.org/pub/pdb/validation_reports/ol/8ol5 | HTTPS FTP |
-Related structure data
Related structure data | 16949MC 8ol2C 8ol3C 8ol6C 8ol7C 8olgC 8olnC 8oloC 8olqC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein/peptide | Mass: 4520.087 Da / Num. of mol.: 10 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: APP, A4, AD1 / Organ: Brain / Production host: Mus musculus (house mouse) / Strain (production host): ARTE10 / References: UniProt: P05067 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: Amyloid fibril of amyloid-beta / Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Molecular weight | Value: 20 kDa/nm / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Mus musculus (house mouse) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9521 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -3.21 ° / Axial rise/subunit: 4.76 Å / Axial symmetry: C2 | ||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 226920 / Algorithm: FOURIER SPACE / Symmetry type: HELICAL |