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Yorodumi- EMDB-16027: Murine amyloid-beta filaments with the Arctic mutation (E22G) fro... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16027 | |||||||||
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Title | Murine amyloid-beta filaments with the Arctic mutation (E22G) from APP(NL-G-F) mouse brains | ABeta | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Amyloid / amyloid-beta / Arctic mutation / APP / NL-G-F / mouse brains / filaments / E22G / E693G / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information regulation of response to calcium ion / Formyl peptide receptors bind formyl peptides and many other ligands / growth cone lamellipodium / Advanced glycosylation endproduct receptor signaling / cellular response to norepinephrine stimulus / growth cone filopodium / ECM proteoglycans / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / TRAF6 mediated NF-kB activation / Lysosome Vesicle Biogenesis ...regulation of response to calcium ion / Formyl peptide receptors bind formyl peptides and many other ligands / growth cone lamellipodium / Advanced glycosylation endproduct receptor signaling / cellular response to norepinephrine stimulus / growth cone filopodium / ECM proteoglycans / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / TRAF6 mediated NF-kB activation / Lysosome Vesicle Biogenesis / ion binding / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Post-translational protein phosphorylation / G alpha (q) signalling events / TAK1-dependent IKK and NF-kappa-B activation / G alpha (i) signalling events / response to yeast / Platelet degranulation / peptidase activator activity / growth factor receptor binding / Mitochondrial protein degradation / antifungal humoral response / astrocyte projection / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / 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 / ciliary rootlet / PTB domain binding / Golgi-associated vesicle / main axon / positive regulation of amyloid fibril formation / neuron remodeling / nuclear envelope lumen / suckling behavior / COPII-coated ER to Golgi transport vesicle / dendrite development / neuronal dense core vesicle / presynaptic active zone / modulation of excitatory postsynaptic potential / neuromuscular process controlling balance / 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 / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / positive regulation of calcium-mediated signaling / positive regulation of chemokine production / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / forebrain development / Notch signaling pathway / neuron projection maintenance / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / positive regulation of glycolytic process / ionotropic glutamate receptor signaling pathway / response to interleukin-1 / cholesterol metabolic process / positive regulation of mitotic cell cycle / extracellular matrix organization / adult locomotory behavior / axonogenesis / positive regulation of peptidyl-threonine phosphorylation / positive regulation of interleukin-1 beta production / dendritic shaft / positive regulation of long-term synaptic potentiation / central nervous system development / locomotory behavior / long-term synaptic potentiation / positive regulation of JNK cascade / microglial cell activation / regulation of long-term neuronal synaptic plasticity / serine-type endopeptidase inhibitor activity / visual learning / neuromuscular junction / recycling endosome / neuron differentiation / memory / cognition / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / cellular response to amyloid-beta / antimicrobial humoral immune response mediated by antimicrobial peptide / positive regulation of interleukin-6 production / G2/M transition of mitotic cell cycle Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Yang Y / Zhang WJ / Murzin AG / Schweighauser M / Huang M / Lovestam SKA / Peak-Chew SY / Macdonald J / Lavenir I / Ghetti B ...Yang Y / Zhang WJ / Murzin AG / Schweighauser M / Huang M / Lovestam SKA / Peak-Chew SY / Macdonald J / Lavenir I / Ghetti B / Graff C / Kumar A / Nordber A / Goedert M / Scheres SHW | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Acta Neuropathol / Year: 2023 Title: Cryo-EM structures of amyloid-β filaments with the Arctic mutation (E22G) from human and mouse brains. Authors: Yang Yang / Wenjuan Zhang / Alexey G Murzin / Manuel Schweighauser / Melissa Huang / Sofia Lövestam / Sew Y Peak-Chew / Takashi Saito / Takaomi C Saido / Jennifer Macdonald / Isabelle ...Authors: Yang Yang / Wenjuan Zhang / Alexey G Murzin / Manuel Schweighauser / Melissa Huang / Sofia Lövestam / Sew Y Peak-Chew / Takashi Saito / Takaomi C Saido / Jennifer Macdonald / Isabelle Lavenir / Bernardino Ghetti / Caroline Graff / Amit Kumar / Agneta Nordberg / Michel Goedert / Sjors H W Scheres / Abstract: The Arctic mutation, encoding E693G in the amyloid precursor protein (APP) gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer's disease. Here, we report the high-resolution cryo- ...The Arctic mutation, encoding E693G in the amyloid precursor protein (APP) gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer's disease. Here, we report the high-resolution cryo-EM structures of Aβ filaments from the frontal cortex of a previously described case (AβPParc1) with the Arctic mutation. Most filaments consist of two pairs of non-identical protofilaments that comprise residues V12-V40 (human Arctic fold A) and E11-G37 (human Arctic fold B). They have a substructure (residues F20-G37) in common with the folds of type I and type II Aβ42. When compared to the structures of wild-type Aβ42 filaments, there are subtle conformational changes in the human Arctic folds, because of the lack of a side chain at G22, which may strengthen hydrogen bonding between mutant Aβ molecules and promote filament formation. A minority of Aβ42 filaments of type II was also present, as were tau paired helical filaments. In addition, we report the cryo-EM structures of Aβ filaments with the Arctic mutation from mouse knock-in line App. Most filaments are made of two identical mutant protofilaments that extend from D1 to G37 (App murine Arctic fold). In a minority of filaments, two dimeric folds pack against each other in an anti-parallel fashion. The App murine Arctic fold differs from the human Arctic folds, but shares some substructure. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16027.map.gz | 9.3 MB | EMDB map data format | |
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Header (meta data) | emd-16027-v30.xml emd-16027.xml | 14.7 KB 14.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16027_fsc.xml | 7.2 KB | Display | FSC data file |
Images | emd_16027.png | 153.2 KB | ||
Masks | emd_16027_msk_1.map | 30.5 MB | Mask map | |
Filedesc metadata | emd-16027.cif.gz | 4.9 KB | ||
Others | emd_16027_half_map_1.map.gz emd_16027_half_map_2.map.gz | 9.2 MB 9.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16027 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16027 | HTTPS FTP |
-Validation report
Summary document | emd_16027_validation.pdf.gz | 731.8 KB | Display | EMDB validaton report |
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Full document | emd_16027_full_validation.pdf.gz | 731.4 KB | Display | |
Data in XML | emd_16027_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | emd_16027_validation.cif.gz | 18 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16027 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16027 | HTTPS FTP |
-Related structure data
Related structure data | 8bg9MC 8bfzC 8bg0C 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_16027.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.204 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_16027_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_16027_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_16027_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Amyloid-beta filaments extracted from the mouse brains with APP N...
Entire | Name: Amyloid-beta filaments extracted from the mouse brains with APP NL-G-F mutations |
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Components |
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-Supramolecule #1: Amyloid-beta filaments extracted from the mouse brains with APP N...
Supramolecule | Name: Amyloid-beta filaments extracted from the mouse brains with APP NL-G-F mutations type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Amyloid-beta protein 40
Macromolecule | Name: Amyloid-beta protein 40 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 4.080538 KDa |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVG 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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Image recording | Film or detector model: GATAN K3 (6k 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 / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |