+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13809 | |||||||||||||||||||||
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Title | Type II 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 / : / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / presynaptic active zone / nuclear envelope lumen / modulation of excitatory postsynaptic potential / suckling behavior / COPII-coated ER to Golgi transport vesicle / dendrite development / smooth endoplasmic reticulum / regulation of NMDA receptor activity / TRAF6 mediated NF-kB activation / negative regulation of long-term synaptic potentiation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / 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 / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / neuron projection maintenance / positive regulation of glycolytic process / extracellular matrix organization / response to interleukin-1 / positive regulation of mitotic cell cycle / axonogenesis / 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 / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / neuromuscular junction / visual learning / serine-type endopeptidase inhibitor activity / recycling endosome / cognition / positive regulation of inflammatory response / positive regulation of interleukin-6 production / neuron cellular homeostasis / Golgi lumen / endocytosis / 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) / cellular response to amyloid-beta / neuron projection development / 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: 2.8 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 States, 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_13809.map.gz | 22 MB | EMDB map data format | |
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Header (meta data) | emd-13809-v30.xml emd-13809.xml | 16.2 KB 16.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_13809_fsc.xml | 9.2 KB | Display | FSC data file |
Images | emd_13809.png | 43.4 KB | ||
Others | emd_13809_half_map_1.map.gz emd_13809_half_map_2.map.gz | 21.1 MB 21.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13809 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13809 | HTTPS FTP |
-Related structure data
Related structure data | 7q4mMC 7q4bC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10917 (Title: Single particle cryo-EM dataset of sarkosyl-insoluble fraction from the frontal cortex of an individual with pathological aging of amyloid-β 42 filaments Data size: 203.1 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_13809.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: 0.73 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_13809_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_13809_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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-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: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |