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Open data
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Basic information
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| Title | Type IIIb beta-amyloid 40 Filaments from Down Syndrome | |||||||||
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Keywords | Beta Amyloid filaments / Down Syndrome / NEUROPEPTIDE / Human Trisomy 21 | |||||||||
| Function / homology | Function and homology informationamyloid-beta complex / growth cone lamellipodium / cellular response to norepinephrine stimulus / collateral sprouting in absence of injury / growth cone filopodium / microglia development / hippocampal neuron apoptotic process / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport ...amyloid-beta complex / growth cone lamellipodium / cellular response to norepinephrine stimulus / collateral sprouting in absence of injury / growth cone filopodium / microglia development / hippocampal neuron apoptotic process / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / axon midline choice point recognition / regulation of synapse structure or activity / positive regulation of synaptic transmission, cholinergic / astrocyte activation involved in immune response / NMDA selective glutamate receptor signaling pathway / regulation of spontaneous synaptic transmission / mating behavior / growth factor receptor binding / peptidase activator activity / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / PTB domain binding / astrocyte projection / Golgi-associated vesicle / neuron remodeling / Lysosome Vesicle Biogenesis / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / regulation of multicellular organism growth / dendrite development / nuclear envelope lumen / TRAF6 mediated NF-kB activation / positive regulation of protein metabolic process / signaling receptor activator activity / negative regulation of long-term synaptic potentiation / transition metal ion binding / Advanced glycosylation endproduct receptor signaling / The NLRP3 inflammasome / intracellular copper ion homeostasis / modulation of excitatory postsynaptic potential / Notch signaling pathway / main axon / ECM proteoglycans / response to insulin-like growth factor stimulus / positive regulation of T cell migration / regulation of presynapse assembly / extracellular matrix organization / swimming behavior / neuronal dense core vesicle / adult locomotory behavior / regulation of long-term neuronal synaptic plasticity / Purinergic signaling in leishmaniasis infection / positive regulation of chemokine production / positive regulation of calcium-mediated signaling / positive regulation of mitotic cell cycle / axonogenesis / cellular response to manganese ion / neuron projection maintenance / clathrin-coated pit / astrocyte activation / visual learning / cellular response to cAMP / synaptic cleft / regulation of neuron apoptotic process / positive regulation of glycolytic process / Mitochondrial protein degradation / platelet alpha granule lumen / ionotropic glutamate receptor signaling pathway / response to interleukin-1 / learning / locomotory behavior / cellular response to copper ion / endosome lumen / trans-Golgi network membrane / positive regulation of interleukin-1 beta production / dendritic shaft / central nervous system development / positive regulation of long-term synaptic potentiation / protein serine/threonine kinase binding / Post-translational protein phosphorylation / serine-type endopeptidase inhibitor activity / microglial cell activation / cellular response to nerve growth factor stimulus / positive regulation of non-canonical NF-kappaB signal transduction / synapse organization / positive regulation of interleukin-6 production / TAK1-dependent IKK and NF-kappa-B activation / positive regulation of JNK cascade / recycling endosome / response to lead ion / Golgi lumen / endocytosis / cognition / 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 inflammatory response / calcium ion transport / positive regulation of tumor necrosis factor production / regulation of gene expression / regulation of translation Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | helical reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Hoq MR / Vago FS / Bharath SR / Jiang W | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024Title: 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. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_40421.map.gz | 4.5 MB | EMDB map data format | |
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| Header (meta data) | emd-40421-v30.xml emd-40421.xml | 13.9 KB 13.9 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_40421_fsc.xml | 10.7 KB | Display | FSC data file |
| Images | emd_40421.png | 70.7 KB | ||
| Filedesc metadata | emd-40421.cif.gz | 5 KB | ||
| Others | emd_40421_half_map_1.map.gz emd_40421_half_map_2.map.gz | 79.5 MB 79.7 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40421 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40421 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8selMC ![]() 8sehC ![]() 8seiC ![]() 8sejC ![]() 8sekC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_40421.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.054 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #2
| File | emd_40421_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #1
| File | emd_40421_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : Type IIIb beta amyloid 40 from Human trisomy 21 Case 2.
| Entire | Name: Type IIIb beta amyloid 40 from Human trisomy 21 Case 2. |
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| Components |
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-Supramolecule #1: Type IIIb beta amyloid 40 from Human trisomy 21 Case 2.
| Supramolecule | Name: Type IIIb beta amyloid 40 from Human trisomy 21 Case 2. type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Amyloid-beta protein 40
| Macromolecule | Name: Amyloid-beta protein 40 / type: protein_or_peptide / ID: 1 Details: Type IIIb beta-amyloid 40 Filaments from Human Trisomy 21 Number of copies: 20 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 4.335852 KDa |
| Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV UniProtKB: Amyloid-beta precursor protein |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | helical reconstruction |
| Aggregation state | filament |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: DIRECT ELECTRON DE-12 (4k x 3k) / Detector mode: COUNTING / Average electron dose: 52.35 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.4 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN


