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Yorodumi- EMDB-29037: Amyloid-beta (1-40) fibrils derived from familial Dutch-type CAA ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29037 | |||||||||
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Title | Amyloid-beta (1-40) fibrils derived from familial Dutch-type CAA patient (population B) | |||||||||
Map data | Final sharpened map. | |||||||||
Sample |
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Keywords | amyloid / vascular / fibril / human / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information NMDA selective glutamate receptor signaling pathway / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / signaling receptor activator activity ...NMDA selective glutamate receptor signaling pathway / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / 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 / Lysosome Vesicle Biogenesis / ciliary rootlet / 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 / neuromuscular process controlling balance / Advanced glycosylation endproduct receptor signaling / transition metal ion binding / regulation of presynapse assembly / negative regulation of long-term synaptic potentiation / negative regulation of neuron differentiation / regulation of multicellular organism growth / intracellular copper ion homeostasis / ECM proteoglycans / trans-Golgi network membrane / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / clathrin-coated pit / protein serine/threonine kinase binding / regulation of peptidyl-tyrosine phosphorylation / 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 / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / response to interleukin-1 / positive regulation of glycolytic process / axonogenesis / positive regulation of mitotic cell cycle / extracellular matrix organization / adult locomotory behavior / platelet alpha granule lumen / positive regulation of interleukin-1 beta production / learning / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / positive regulation of long-term synaptic potentiation / cognition / 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 / serine-type endopeptidase inhibitor activity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / recycling endosome / positive regulation of interleukin-6 production / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / cellular response to amyloid-beta / positive regulation of tumor necrosis factor production / G2/M transition of mitotic cell cycle / neuron projection development / cell-cell junction / Platelet degranulation / synaptic vesicle / apical part of cell Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.09 Å | |||||||||
Authors | Crooks EJ / Fu Z / Chowdury S / Smith SO | |||||||||
Funding support | United States, 2 items
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Citation | Journal: J Struct Biol / Year: 2024 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 | emd_29037.map.gz | 50.7 MB | EMDB map data format | |
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Header (meta data) | emd-29037-v30.xml emd-29037.xml | 17.5 KB 17.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_29037_fsc.xml | 8.7 KB | Display | FSC data file |
Images | emd_29037.png | 227.1 KB | ||
Masks | emd_29037_msk_1.map | 56.8 MB | Mask map | |
Filedesc metadata | emd-29037.cif.gz | 5.5 KB | ||
Others | emd_29037_half_map_1.map.gz emd_29037_half_map_2.map.gz | 43.7 MB 43.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29037 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29037 | HTTPS FTP |
-Validation report
Summary document | emd_29037_validation.pdf.gz | 672.1 KB | Display | EMDB validaton report |
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Full document | emd_29037_full_validation.pdf.gz | 671.6 KB | Display | |
Data in XML | emd_29037_validation.xml.gz | 14.5 KB | Display | |
Data in CIF | emd_29037_validation.cif.gz | 20.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29037 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29037 | HTTPS FTP |
-Related structure data
Related structure data | 8ff3MC 8ff2C C: citing same article (ref.) M: atomic model generated by this map |
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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_29037.map.gz / Format: CCP4 / Size: 56.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Final sharpened map. | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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
File | emd_29037_msk_1.map | ||||||||||||
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Projections & Slices |
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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. | ||||||||||||
Projections & Slices |
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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. | ||||||||||||
Projections & Slices |
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Density Histograms |
-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: Homo sapiens (human) / Organ: Brain / Tissue: Vasculature |
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: 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 |
-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 |
-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: FIELD EMISSION GUN |
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 |
+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: |