+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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Function / homology | Function and homology information regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / smooth endoplasmic reticulum calcium ion homeostasis ...regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / smooth endoplasmic reticulum calcium ion homeostasis / axon midline choice point recognition / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / regulation of Wnt signaling pathway / mating behavior / positive regulation of amyloid fibril formation / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / neuron remodeling / Golgi-associated vesicle / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / presynaptic active zone / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / : / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / modulation of excitatory postsynaptic potential / suckling behavior / dendrite development / smooth endoplasmic reticulum / regulation of NMDA receptor activity / TRAF6 mediated NF-kB activation / negative regulation of long-term synaptic potentiation / neuromuscular process controlling balance / Advanced glycosylation endproduct receptor signaling / regulation of presynapse assembly / The NLRP3 inflammasome / intracellular copper ion homeostasis / transition metal ion binding / regulation of multicellular organism growth / negative regulation of neuron differentiation / ECM proteoglycans / spindle midzone / positive regulation of T cell migration / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / forebrain development / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / clathrin-coated pit / Notch signaling pathway / cholesterol metabolic process / positive regulation of G2/M transition of mitotic cell cycle / ionotropic glutamate receptor signaling pathway / positive regulation of protein metabolic process / neuron projection maintenance / positive regulation of glycolytic process / extracellular matrix organization / response to interleukin-1 / axonogenesis / positive regulation of mitotic cell cycle / adult locomotory behavior / dendritic shaft / trans-Golgi network membrane / locomotory behavior / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation / learning / positive regulation of interleukin-1 beta production / central nervous system development / positive regulation of long-term synaptic potentiation / astrocyte activation / endosome lumen / Post-translational protein phosphorylation / synapse organization / positive regulation of JNK cascade / microglial cell activation / visual learning / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / neuromuscular junction / serine-type endopeptidase inhibitor activity / cognition / recycling endosome / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of interleukin-6 production / Golgi lumen / 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) / neuron projection development / cellular response to amyloid-beta / positive regulation of DNA-binding transcription factor activity / G2/M transition of mitotic cell cycle / cell-cell junction / synaptic vesicle / positive regulation of tumor necrosis factor production / regulation of translation Similarity search - Function | |||||||||||||||||||||
Biological species | Homo sapiens (human) / Human (human) | |||||||||||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||||||||||||||
Authors | Yang Y / Arseni D / Zhang W / Huang M / Lovestam SKA / Schweighauser M / Kotecha A / Murzin AG / Peak-Chew SY / Macdonald J ...Yang Y / Arseni D / Zhang W / Huang M / Lovestam SKA / Schweighauser M / Kotecha A / Murzin AG / Peak-Chew SY / Macdonald J / Lavenir I / Garringer HJ / Gelpi E / Newell KL / Kovacs GG / Vidal R / Ghetti B / Falcon B / Scheres SHW / Goedert M | |||||||||||||||||||||
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 | 16.5 KB 16.5 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 | ||
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 |
-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: Human (human) |
Molecular weight | Theoretical: 4.520087 KDa |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IA |
-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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |