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- EMDB-29037: Amyloid-beta (1-40) fibrils derived from familial Dutch-type CAA ... -
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Open data
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Basic information
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Title | Amyloid-beta (1-40) fibrils derived from familial Dutch-type CAA patient (population B) | |||||||||
![]() | Final sharpened map. | |||||||||
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![]() | amyloid / vascular / fibril / human / 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 / 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 | ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.09 Å | |||||||||
![]() | Crooks EJ / Fu Z / Chowdury S / Smith SO | |||||||||
Funding support | ![]()
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![]() | ![]() Title: An electrostatic cluster guides Aβ40 fibril formation in sporadic and Dutch-type cerebral amyloid angiopathy. Authors: Ziao Fu / Elliot J Crooks / Brandon A Irizarry / Xiaoyue Zhu / Saikat Chowdhury / William E Van Nostrand / Steven O Smith / ![]() ![]() Abstract: Cerebral amyloid angiopathy (CAA) is associated with the accumulation of fibrillar Aβ peptides upon and within the cerebral vasculature, which leads to loss of vascular integrity and contributes to ...Cerebral amyloid angiopathy (CAA) is associated with the accumulation of fibrillar Aβ peptides upon and within the cerebral vasculature, which leads to loss of vascular integrity and contributes to disease progression in Alzheimer's disease (AD). We investigate the structure of human-derived Aβ40 fibrils obtained from patients diagnosed with sporadic or familial Dutch-type (E22Q) CAA. Using cryo-EM, two primary structures are identified containing elements that have not been observed in in vitro Aβ40 fibril structures. One population has an ordered N-terminal fold comprised of two β-strands stabilized by electrostatic interactions involving D1, E22, D23 and K28. This charged cluster is disrupted in the second population, which exhibits a disordered N-terminus and is favored in fibrils derived from the familial Dutch-type CAA patient. These results illustrate differences between human-derived CAA and AD fibrils, and how familial CAA mutations can guide fibril formation. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 50.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.5 KB 17.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.7 KB | Display | ![]() |
Images | ![]() | 227.1 KB | ||
Masks | ![]() | 56.8 MB | ![]() | |
Filedesc metadata | ![]() | 5.5 KB | ||
Others | ![]() ![]() | 43.7 MB 43.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 672.1 KB | Display | ![]() |
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Full document | ![]() | 671.6 KB | Display | |
Data in XML | ![]() | 14.5 KB | Display | |
Data in CIF | ![]() | 20.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ff3MC ![]() 8ff2C C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Final sharpened map. | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.12 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: Half-map 2.
File | emd_29037_half_map_1.map | ||||||||||||
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Annotation | Half-map 2. | ||||||||||||
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Density Histograms |
-Half map: Half-map 1.
File | emd_29037_half_map_2.map | ||||||||||||
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Annotation | Half-map 1. | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Fibrillar assembly of human Amyloid-beta 1-40 from a familial Dut...
Entire | Name: Fibrillar assembly of human Amyloid-beta 1-40 from a familial Dutch-type cerebral amyloid angiopathy patient |
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Components |
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-Supramolecule #1: Fibrillar assembly of human Amyloid-beta 1-40 from a familial Dut...
Supramolecule | Name: Fibrillar assembly of human Amyloid-beta 1-40 from a familial Dutch-type cerebral amyloid angiopathy patient type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 4.3299 MDa |
-Macromolecule #1: Amyloid-beta precursor protein
Macromolecule | Name: Amyloid-beta precursor protein / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
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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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV |
Details | Templated growth from human-derived vascular amyloid deposits |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Digitization - Frames/image: 1-99 / Number grids imaged: 1 / Number real images: 2140 / Average exposure time: 86.11 sec. / Average electron dose: 56.92 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 92000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Chain ID: A / Chain - Residue range: 10-40 / Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 71.7 |
Output model | ![]() PDB-8ff3: |