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Yorodumi- EMDB-15770: Type I amyloid-beta 42 filaments from high-spin supernatants of a... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-15770 | ||||||||||||
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Title | Type I amyloid-beta 42 filaments from high-spin supernatants of aqueous extracts from Alzheimer's disease brains | ABeta42 | ||||||||||||
Map data | |||||||||||||
Sample |
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Keywords | amyloid / filaments / Abeta42 / amyloid-beta / cryo-EM / PROTEIN FIBRIL | ||||||||||||
Function / homology | Function and homology information regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / collateral sprouting in absence of injury / cytosolic mRNA polyadenylation / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction ...regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / collateral sprouting in absence of injury / cytosolic mRNA polyadenylation / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / regulation of Wnt signaling pathway / 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 / mating behavior / NMDA selective glutamate receptor signaling pathway / Mitochondrial protein degradation / 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 / : / protein serine/threonine kinase binding / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / suckling behavior / modulation of excitatory postsynaptic potential / COPII-coated ER to Golgi transport vesicle / presynaptic active zone / dendrite development / smooth endoplasmic reticulum / 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 / intracellular copper ion homeostasis / regulation of multicellular organism growth / negative regulation of neuron differentiation / negative regulation of long-term synaptic potentiation / ECM proteoglycans / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / forebrain development / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / Notch signaling pathway / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / neuron projection maintenance / cholesterol metabolic process / response to interleukin-1 / extracellular matrix organization / positive regulation of glycolytic process / positive regulation of mitotic cell cycle / axonogenesis / adult locomotory behavior / trans-Golgi network membrane / dendritic shaft / platelet alpha granule lumen / locomotory behavior / 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 / endosome lumen / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / synapse organization / regulation of long-term neuronal synaptic plasticity / microglial cell activation / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / serine-type endopeptidase inhibitor activity / recycling endosome / cognition / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / endocytosis / positive regulation of interleukin-6 production / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to amyloid-beta / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / neuron projection development / G2/M transition of mitotic cell cycle / cell-cell junction / positive regulation of tumor necrosis factor production / synaptic vesicle Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / human (human) | ||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 2.9 Å | ||||||||||||
Authors | Yang Y / Stern MA / Meunier LA / Liu W / Cai YQ / Ericsson M / Liu L / Selkoe JD / Goedert M / Scheres HWS | ||||||||||||
Funding support | United Kingdom, 3 items
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Citation | Journal: Neuron / Year: 2023 Title: Abundant Aβ fibrils in ultracentrifugal supernatants of aqueous extracts from Alzheimer's disease brains. Authors: Andrew M Stern / Yang Yang / Shanxue Jin / Keitaro Yamashita / Angela L Meunier / Wen Liu / Yuqi Cai / Maria Ericsson / Lei Liu / Michel Goedert / Sjors H W Scheres / Dennis J Selkoe / Abstract: Soluble oligomers of amyloid β-protein (Aβ) have been defined as aggregates in supernatants following ultracentrifugation of aqueous extracts from Alzheimer's disease (AD) brains and are believed ...Soluble oligomers of amyloid β-protein (Aβ) have been defined as aggregates in supernatants following ultracentrifugation of aqueous extracts from Alzheimer's disease (AD) brains and are believed to be upstream initiators of synaptic dysfunction, but little is known about their structures. We now report the unexpected presence of Aβ fibrils in synaptotoxic high-speed supernatants from AD brains extracted by soaking in an aqueous buffer. The fibrils did not appear to form during preparation, and their counts by EM correlated with Aβ ELISA quantification. Cryo-EM structures of aqueous Aβ fibrils were identical to those from sarkosyl-insoluble homogenates. The fibrils in aqueous extracts were labeled by lecanemab, an Aβ aggregate-directed antibody reported to improve AD cognitive outcomes. Lecanemab provided protection against aqueous fibril synaptotoxicity. We conclude that fibrils are abundant in aqueous extracts from AD brains and have the same structures as those from plaques. These findings have implications for AD pathogenesis and drug design. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_15770.map.gz | 25.2 MB | EMDB map data format | |
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Header (meta data) | emd-15770-v30.xml emd-15770.xml | 14.5 KB 14.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_15770_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_15770.png | 107 KB | ||
Masks | emd_15770_msk_1.map | 64 MB | Mask map | |
Others | emd_15770_half_map_1.map.gz emd_15770_half_map_2.map.gz | 25.2 MB 25.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-15770 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-15770 | HTTPS FTP |
-Related structure data
Related structure data | 8azsMC 8aztC 8azuC M: atomic model generated by this map C: citing same article (ref.) |
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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_15770.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: 0.831 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_15770_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_15770_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_15770_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Type I amyloid-beta 42 filaments in soluble high-molecular weight...
Entire | Name: Type I amyloid-beta 42 filaments in soluble high-molecular weight aggregate fractions extracted from Alzheimer's disease brain |
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Components |
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-Supramolecule #1: Type I amyloid-beta 42 filaments in soluble high-molecular weight...
Supramolecule | Name: Type I amyloid-beta 42 filaments in soluble high-molecular weight aggregate fractions extracted from Alzheimer's disease brain type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all |
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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: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: human (human) |
Molecular weight | Theoretical: 4.520087 KDa |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IA 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: 7.5 |
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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 / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.0 µm |
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 |