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Yorodumi- EMDB-46424: Type Id amyloid-beta 42 filaments in dominantly inherited Alzheim... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-46424 | |||||||||
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Title | Type Id amyloid-beta 42 filaments in dominantly inherited Alzheimer disease with cotton wool plaques | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Amyloid filaments / cotton wool plaques / neurodegeneration / NEUROPEPTIDE / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / NMDA selective glutamate receptor signaling pathway / microglia development / regulation of Wnt signaling pathway / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity ...cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / NMDA selective glutamate receptor signaling pathway / microglia development / regulation of Wnt signaling pathway / regulation of synapse structure or activity / 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 / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / Golgi-associated vesicle / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / COPII-coated ER to Golgi transport vesicle / suckling behavior / nuclear envelope lumen / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / The NLRP3 inflammasome / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / negative regulation of long-term synaptic potentiation / regulation of presynapse assembly / transition metal ion binding / regulation of multicellular organism growth / negative regulation of neuron differentiation / intracellular copper ion homeostasis / ECM proteoglycans / positive regulation of T cell migration / spindle midzone / smooth endoplasmic reticulum / Purinergic signaling in leishmaniasis infection / protein serine/threonine kinase binding / regulation of peptidyl-tyrosine phosphorylation / clathrin-coated pit / positive regulation of chemokine production / forebrain development / Notch signaling pathway / neuron projection maintenance / Mitochondrial protein degradation / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / cholesterol metabolic process / ionotropic glutamate receptor signaling pathway / positive regulation of calcium-mediated signaling / positive regulation of glycolytic process / response to interleukin-1 / extracellular matrix organization / positive regulation of mitotic cell cycle / axonogenesis / adult locomotory behavior / platelet alpha granule lumen / trans-Golgi network membrane / positive regulation of interleukin-1 beta production / learning / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / positive regulation of long-term synaptic potentiation / central nervous system development / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / regulation of long-term neuronal synaptic plasticity / synapse organization / TAK1-dependent IKK and NF-kappa-B activation / serine-type endopeptidase inhibitor activity / neuromuscular junction / visual learning / recycling endosome / cognition / Golgi lumen / positive regulation of inflammatory response / positive regulation of interleukin-6 production / neuron cellular homeostasis / 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) / endocytosis / cellular response to amyloid-beta / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle / Platelet degranulation / apical part of cell Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Hoq MR / Vago FS / Ozcan KA / Bharath SR | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Acta Neuropathol / Year: 2024 Title: Cryo-EM structures of cotton wool plaques' amyloid β and of tau filaments in dominantly inherited Alzheimer disease. Authors: Md Rejaul Hoq / Anllely Fernandez / Frank S Vago / Grace I Hallinan / Sakshibeedu R Bharath / Daoyi Li / Kadir A Ozcan / Holly J Garringer / Wen Jiang / Ruben Vidal / Bernardino Ghetti / Abstract: Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the ...Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the presenilin 1 (PSEN1) gene. CWPs are round, eosinophilic amyloid-β (Aβ) plaques that lack an amyloid core and are recognizable, but not fluorescent, in Thioflavin S (ThS) preparations. Amino-terminally truncated and post-translationally modified Aβ peptide species are the main component of CWPs. Tau immunopositive neurites may be present in CWPs. In addition, neurofibrillary tangles coexist with CWPs. Herein, we report the structure of Aβ and tau filaments isolated from brain tissue of individuals affected by DIAD caused by the PSEN1 V261I and A431E mutations, with the CWP neuropathologic phenotype. CWPs are predominantly composed of type I Aβ filaments present in two novel arrangements, type Ic and type Id; additionally, CWPs contain type I and type Ib Aβ filaments. Tau filaments have the AD fold, which has been previously reported in sporadic AD and DIAD. The formation of type Ic and type Id Aβ filaments may be the basis for the phenotype of CWPs. Our data are relevant for the development of PET imaging methodologies to best detect CWPs in DIAD. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_46424.map.gz | 75.7 MB | EMDB map data format | |
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Header (meta data) | emd-46424-v30.xml emd-46424.xml | 16.1 KB 16.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_46424_fsc.xml | 9.8 KB | Display | FSC data file |
Images | emd_46424.png | 68.7 KB | ||
Masks | emd_46424_msk_1.map | 83.7 MB | Mask map | |
Filedesc metadata | emd-46424.cif.gz | 5.3 KB | ||
Others | emd_46424_half_map_1.map.gz emd_46424_half_map_2.map.gz | 65.4 MB 65.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-46424 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-46424 | HTTPS FTP |
-Validation report
Summary document | emd_46424_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_46424_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_46424_validation.xml.gz | 17.7 KB | Display | |
Data in CIF | emd_46424_validation.cif.gz | 23.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-46424 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-46424 | HTTPS FTP |
-Related structure data
Related structure data | 9czpMC 9cziC 9czlC 9cznC 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_46424.map.gz / Format: CCP4 / Size: 83.7 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
-Mask #1
File | emd_46424_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_46424_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_46424_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Type Id amyloid-beta 42
Entire | Name: Type Id amyloid-beta 42 |
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Components |
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-Supramolecule #1: Type Id amyloid-beta 42
Supramolecule | Name: Type Id amyloid-beta 42 / type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Amyloid-beta protein 42
Macromolecule | Name: Amyloid-beta protein 42 / type: protein_or_peptide / ID: 1 / Number of copies: 20 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 3.560128 KDa |
Sequence | String: GYEVHHQKLV FFAEDVGSNK GAIIGLMVGG VVIA 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 Component:
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Vitrification | Cryogen name: ETHANE / Instrument: GATAN CRYOPLUNGE 3 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 2 / Number real images: 23764 / Average exposure time: 3.21 sec. / Average electron dose: 57.79 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-9czp: |