+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0405 | |||||||||||||||
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Title | Amyloid-Beta (20-34) with L-isoaspartate 23 | |||||||||||||||
Map data | ||||||||||||||||
Sample |
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Function / homology | Function and homology information cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / axo-dendritic transport / regulation of Wnt signaling pathway / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / signaling receptor activator activity / axon midline choice point recognition ...cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / axo-dendritic transport / regulation of Wnt signaling pathway / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / signaling receptor activator activity / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / NMDA selective glutamate receptor signaling pathway / Lysosome Vesicle Biogenesis / ciliary rootlet / PTB domain binding / Golgi-associated vesicle / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / suckling behavior / dendrite development / 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 / transition metal ion binding / regulation of presynapse assembly / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / negative regulation of neuron differentiation / intracellular copper ion homeostasis / ECM proteoglycans / trans-Golgi network membrane / positive regulation of T cell migration / smooth endoplasmic reticulum / spindle midzone / Purinergic signaling in leishmaniasis infection / clathrin-coated pit / protein serine/threonine kinase binding / positive regulation of chemokine production / regulation of peptidyl-tyrosine phosphorylation / forebrain development / Notch signaling pathway / neuron projection maintenance / Mitochondrial protein degradation / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / positive regulation of calcium-mediated signaling / 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 / axonogenesis / adult locomotory behavior / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation / positive regulation of interleukin-1 beta production / dendritic shaft / learning / cognition / positive regulation of long-term synaptic potentiation / central nervous system development / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / synapse organization / serine-type endopeptidase inhibitor activity / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / recycling endosome / positive regulation of interleukin-6 production / Golgi lumen / neuron cellular homeostasis / positive regulation of inflammatory response / 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) / cellular response to amyloid-beta / positive regulation of tumor necrosis factor production / G2/M transition of mitotic cell cycle / cell-cell junction / neuron projection development / Platelet degranulation / apical part of cell / synaptic vesicle Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | electron crystallography / cryo EM | |||||||||||||||
Authors | Sawaya MR / Warmack RA / Boyer DR / Zee CT / Richards LS / Cascio D / Gonen T / Clarke SG / Eisenberg DS | |||||||||||||||
Funding support | United States, 4 items
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Citation | Journal: Nat Commun / Year: 2019 Title: Structure of amyloid-β (20-34) with Alzheimer's-associated isomerization at Asp23 reveals a distinct protofilament interface. Authors: Rebeccah A Warmack / David R Boyer / Chih-Te Zee / Logan S Richards / Michael R Sawaya / Duilio Cascio / Tamir Gonen / David S Eisenberg / Steven G Clarke / Abstract: Amyloid-β (Aβ) harbors numerous posttranslational modifications (PTMs) that may affect Alzheimer's disease (AD) pathogenesis. Here we present the 1.1 Å resolution MicroED structure of an Aβ 20- ...Amyloid-β (Aβ) harbors numerous posttranslational modifications (PTMs) that may affect Alzheimer's disease (AD) pathogenesis. Here we present the 1.1 Å resolution MicroED structure of an Aβ 20-34 fibril with and without the disease-associated PTM, L-isoaspartate, at position 23 (L-isoAsp23). Both wild-type and L-isoAsp23 protofilaments adopt β-helix-like folds with tightly packed cores, resembling the cores of full-length fibrillar Aβ structures, and both self-associate through two distinct interfaces. One of these is a unique Aβ interface strengthened by the isoaspartyl modification. Powder diffraction patterns suggest a similar structure may be adopted by protofilaments of an analogous segment containing the heritable Iowa mutation, Asp23Asn. Consistent with its early onset phenotype in patients, Asp23Asn accelerates aggregation of Aβ 20-34, as does the L-isoAsp23 modification. These structures suggest that the enhanced amyloidogenicity of the modified Aβ segments may also reduce the concentration required to achieve nucleation and therefore help spur the pathogenesis of AD. | |||||||||||||||
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_0405.map.gz | 435.1 KB | EMDB map data format | |
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Header (meta data) | emd-0405-v30.xml emd-0405.xml | 14.3 KB 14.3 KB | Display Display | EMDB header |
Images | emd_0405.png | 302 KB | ||
Filedesc structureFactors | emd_0405_sf.cif.gz | 103.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0405 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0405 | HTTPS FTP |
-Validation report
Summary document | emd_0405_validation.pdf.gz | 313.2 KB | Display | EMDB validaton report |
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Full document | emd_0405_full_validation.pdf.gz | 312.8 KB | Display | |
Data in XML | emd_0405_validation.xml.gz | 4.3 KB | Display | |
Data in CIF | emd_0405_validation.cif.gz | 4.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0405 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0405 | HTTPS FTP |
-Related structure data
Related structure data | 6nb9MC 6oizC 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_0405.map.gz / Format: CCP4 / Size: 473.6 KB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X: 0.2704 Å / Y: 0.2435 Å / Z: 0.2923 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : crystal of amyloid-beta residues 20-34 with L-isoaspartate at pos...
Entire | Name: crystal of amyloid-beta residues 20-34 with L-isoaspartate at position 23 |
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Components |
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-Supramolecule #1: crystal of amyloid-beta residues 20-34 with L-isoaspartate at pos...
Supramolecule | Name: crystal of amyloid-beta residues 20-34 with L-isoaspartate at position 23 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Molecular weight | Theoretical: 6.21 kDa/nm |
-Macromolecule #1: Amyloid-beta A4 protein
Macromolecule | Name: Amyloid-beta A4 protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 1.491666 KDa |
Sequence | String: FAE(IAS)VGSNKG AIIGL |
-Macromolecule #2: water
Macromolecule | Name: water / type: ligand / ID: 2 / Number of copies: 4 / 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 | electron crystallography |
Aggregation state | 3D array |
-Sample preparation
Concentration | 2.5 mg/mL |
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Buffer | pH: 7.6 / Component - Name: water |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Support film - Film thickness: 30.0 nm / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber temperature: 100 K / Instrument: FEI VITROBOT MARK IV |
Details | This sample is a crystal. |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Temperature | Min: 100.0 K / Max: 100.0 K |
Image recording | Film or detector model: FEI CETA (4k x 4k) / Digitization - Dimensions - Width: 2048 pixel / Digitization - Dimensions - Height: 2048 pixel / Number grids imaged: 2 / Number diffraction images: 159 / Average exposure time: 3.0 sec. / Average electron dose: 0.01 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION / Camera length: 1050 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution method: DIFFRACTION PATTERN/LAYERLINES |
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Crystal parameters | Unit cell - A: 29.20 Å / Unit cell - B: 4.87 Å / Unit cell - C: 32.44 Å / Unit cell - γ: 90.000 ° / Unit cell - α: 90.000 ° / Unit cell - β: 101.897 ° / Space group: P 21 |
Crystallography statistics | Number intensities measured: 16529 / Number structure factors: 3946 / Fourier space coverage: 82.7 / R sym: 0.197 / R merge: 0.197 / Overall phase error: 28.4 / Overall phase residual: 0.1 / Phase error rejection criteria: 0.1 / High resolution: 1.05 Å / Shell - Shell ID: 1 / Shell - High resolution: 1.0 Å / Shell - Low resolution: 1.05 Å / Shell - Number structure factors: 315 / Shell - Phase residual: 0.1 / Shell - Fourier space coverage: 41.2 / Shell - Multiplicity: 3.09 |
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: OTHER / Overall B value: 10.135 / Target criteria: maximum liklihood |
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Output model | PDB-6nb9: |