+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13800 | |||||||||||||||||||||
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Title | Type I beta-amyloid 42 Filaments from Human Brain | |||||||||||||||||||||
Map data | ||||||||||||||||||||||
Sample |
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Keywords | amyloid filaments / Abeta42 / human brain / cryo-EM / PROTEIN FIBRIL | |||||||||||||||||||||
Function / homology | Function and homology information 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 / 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 / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / : / suckling behavior / nuclear envelope lumen / dendrite development / COPII-coated ER to Golgi transport vesicle / presynaptic active zone / 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 / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / intracellular copper ion homeostasis / negative regulation of neuron differentiation / ECM proteoglycans / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / protein serine/threonine kinase binding / positive regulation of chemokine production / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / forebrain development / Notch signaling pathway / Mitochondrial protein degradation / neuron projection maintenance / positive regulation of G2/M transition of mitotic cell cycle / 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 / adult locomotory behavior / axonogenesis / platelet alpha granule lumen / trans-Golgi network membrane / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / learning / positive regulation of interleukin-1 beta production / positive regulation of long-term synaptic potentiation / locomotory behavior / central nervous system development / endosome lumen / astrocyte activation / positive regulation of JNK cascade / Post-translational protein phosphorylation / microglial cell activation / synapse organization / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / serine-type endopeptidase inhibitor activity / neuromuscular junction / recycling endosome / cognition / neuron cellular homeostasis / Golgi lumen / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / cellular response to amyloid-beta / G2/M transition of mitotic cell cycle / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of interleukin-6 production / neuron projection development / positive regulation of tumor necrosis factor production / cell-cell junction / synaptic vesicle Similarity search - Function | |||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||||||||||||||
Authors | Yang Y / Arseni D | |||||||||||||||||||||
Funding support | United Kingdom, 6 items
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Citation | Journal: Science / Year: 2022 Title: Cryo-EM structures of amyloid-β 42 filaments from human brains. Authors: Yang Yang / Diana Arseni / Wenjuan Zhang / Melissa Huang / Sofia Lövestam / Manuel Schweighauser / Abhay Kotecha / Alexey G Murzin / Sew Y Peak-Chew / Jennifer Macdonald / Isabelle Lavenir ...Authors: Yang Yang / Diana Arseni / Wenjuan Zhang / Melissa Huang / Sofia Lövestam / Manuel Schweighauser / Abhay Kotecha / Alexey G Murzin / Sew Y Peak-Chew / Jennifer Macdonald / Isabelle Lavenir / Holly J Garringer / Ellen Gelpi / Kathy L Newell / Gabor G Kovacs / Ruben Vidal / Bernardino Ghetti / Benjamin Ryskeldi-Falcon / Sjors H W Scheres / Michel Goedert / Abstract: Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer’s disease. Here, we report the cryo–electron microscopy (cryo-EM) structures of Aβ42 ...Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer’s disease. Here, we report the cryo–electron microscopy (cryo-EM) structures of Aβ42 filaments from human brains. Two structurally related S-shaped protofilament folds give rise to two types of filaments. Type I filaments were found mostly in the brains of individuals with sporadic Alzheimer’s disease, and type II filaments were found in individuals with familial Alzheimer’s disease and other conditions. The structures of Aβ42 filaments from the brain differ from those of filaments assembled in vitro. By contrast, in knock-in mice, Aβ42 deposits were made of type II filaments. Knowledge of Aβ42 filament structures from human brains may lead to the development of inhibitors of assembly and improved imaging agents. | |||||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_13800.map.gz | 22.2 MB | EMDB map data format | |
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Header (meta data) | emd-13800-v30.xml emd-13800.xml | 15.8 KB 15.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_13800_fsc.xml | 9.2 KB | Display | FSC data file |
Images | emd_13800.png | 76.6 KB | ||
Filedesc metadata | emd-13800.cif.gz | 5.1 KB | ||
Others | emd_13800_half_map_1.map.gz emd_13800_half_map_2.map.gz | 22.2 MB 22.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13800 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13800 | HTTPS FTP |
-Validation report
Summary document | emd_13800_validation.pdf.gz | 809.9 KB | Display | EMDB validaton report |
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Full document | emd_13800_full_validation.pdf.gz | 809.4 KB | Display | |
Data in XML | emd_13800_validation.xml.gz | 16.3 KB | Display | |
Data in CIF | emd_13800_validation.cif.gz | 21.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13800 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13800 | HTTPS FTP |
-Related structure data
Related structure data | 7q4bMC 7q4mC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10916 (Title: Single particle cryo-EM dataset of sarkosyl-insoluble fraction from the frontal cortex of an individual with Alzheimer’s disease of amyloid-β 42 filaments Data size: 200.7 Data #1: Unaligned multi-frame movies [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_13800.map.gz / Format: CCP4 / Size: 64 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: 0.727 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #2
File | emd_13800_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_13800_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : beta-amyloid 42 filaments extracted from the human brain with Alz...
Entire | Name: beta-amyloid 42 filaments extracted from the human brain with Alzheimer's disease |
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Components |
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-Supramolecule #1: beta-amyloid 42 filaments extracted from the human brain with Alz...
Supramolecule | Name: beta-amyloid 42 filaments extracted from the human brain with Alzheimer's disease type: tissue / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Amyloid-beta precursor protein
Macromolecule | Name: Amyloid-beta precursor protein / type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 4.520087 KDa |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IA UniProtKB: Amyloid-beta precursor protein |
-Macromolecule #2: UNKNOWN ATOM OR ION
Macromolecule | Name: UNKNOWN ATOM OR ION / type: ligand / ID: 2 / Number of copies: 10 / Formula: UNX |
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-Macromolecule #3: water
Macromolecule | Name: water / type: ligand / ID: 3 / Number of copies: 60 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |