+Open data
-Basic information
Entry | Database: PDB / ID: 8sej | ||||||
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Title | Type I beta-amyloid 42 Filaments from Down syndrome | ||||||
Components | Amyloid-beta protein 42Amyloid beta | ||||||
Keywords | NEUROPEPTIDE / Beta Amyloid filaments / Down Syndrome / Human Trisomy 21 | ||||||
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 / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction ...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 / regulation of Wnt signaling pathway / 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 / mating behavior / NMDA selective glutamate receptor signaling pathway / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / positive regulation of amyloid fibril formation / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / protein serine/threonine kinase binding / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / : / nuclear envelope lumen / suckling behavior / presynaptic active zone / dendrite development / COPII-coated ER to Golgi transport vesicle / 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 / regulation of multicellular organism growth / intracellular copper ion homeostasis / negative regulation of long-term synaptic potentiation / negative regulation of neuron differentiation / ECM proteoglycans / smooth endoplasmic reticulum / Mitochondrial protein degradation / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / forebrain development / Notch signaling pathway / positive regulation of G2/M transition of mitotic cell cycle / neuron projection maintenance / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / cholesterol metabolic process / response to interleukin-1 / positive regulation of mitotic cell cycle / extracellular matrix organization / axonogenesis / adult locomotory behavior / trans-Golgi network membrane / platelet alpha granule lumen / locomotory behavior / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / learning / positive regulation of interleukin-1 beta production / central nervous system development / positive regulation of long-term synaptic potentiation / endosome lumen / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / synapse organization / regulation of long-term neuronal synaptic plasticity / microglial cell activation / TAK1-dependent IKK and NF-kappa-B activation / visual learning / serine-type endopeptidase inhibitor activity / neuromuscular junction / recycling endosome / cognition / positive regulation of inflammatory response / Golgi lumen / neuron cellular homeostasis / endocytosis / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to amyloid-beta / positive regulation of interleukin-6 production / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / neuron projection development / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / cell-cell junction / synaptic vesicle Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.17 Å | ||||||
Authors | Hoq, M.R. / Bharath, S.R. / Vago, F.S. / Jiang, W. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Cryo-EM structures of amyloid-β and tau filaments in Down syndrome. Authors: Anllely Fernandez / Md Rejaul Hoq / Grace I Hallinan / Daoyi Li / Sakshibeedu R Bharath / Frank S Vago / Xiaoqi Zhang / Kadir A Ozcan / Kathy L Newell / Holly J Garringer / Wen Jiang / ...Authors: Anllely Fernandez / Md Rejaul Hoq / Grace I Hallinan / Daoyi Li / Sakshibeedu R Bharath / Frank S Vago / Xiaoqi Zhang / Kadir A Ozcan / Kathy L Newell / Holly J Garringer / Wen Jiang / Bernardino Ghetti / Ruben Vidal / Abstract: Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-β (Aβ) and tau filaments is ...Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-β (Aβ) and tau filaments is unknown. Here we report the structure of Aβ and tau filaments from two DS brains. We found two Aβ filaments (types IIIa and IIIb) that differ from those previously reported in sporadic AD and two types of Aβ filaments (I and II) identical to those found in sporadic and familial AD. Tau filaments (paired helical filaments and straight filaments) were identical to those in AD, supporting the notion of a common mechanism through which amyloids trigger aggregation of tau. This knowledge is important for understanding AD in DS and assessing whether adults with DS could be included in AD clinical trials. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8sej.cif.gz | 63.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8sej.ent.gz | 50.1 KB | Display | PDB format |
PDBx/mmJSON format | 8sej.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/se/8sej ftp://data.pdbj.org/pub/pdb/validation_reports/se/8sej | HTTPS FTP |
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-Related structure data
Related structure data | 40416MC 8sehC 8seiC 8sekC 8selC 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: 3560.128 Da / Num. of mol.: 10 / Source method: isolated from a natural source Details: Type I beta-amyloid 42 filaments from Down syndrome Case 2 Source: (natural) Homo sapiens (human) / 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: Type I beta amyloid 42 / Type: TISSUE / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.2 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | 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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 81000 X / Nominal defocus max: 5000 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 1.103 sec. / Electron dose: 50.46 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software | Name: CTFFIND / Category: CTF correction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Helical symmerty | Angular rotation/subunit: 178.24 ° / Axial rise/subunit: 2.38 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 45575 / Symmetry type: HELICAL |