+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8720 | |||||||||
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Title | VGSNKGAIIGL from Amyloid Beta determined by MicroED | |||||||||
Map data | VGSNKGAIIGL from Amyloid Beta | |||||||||
Sample |
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Keywords | Amyloid / steric zipper / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity ...regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / 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 / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / positive regulation of G2/M transition of mitotic cell cycle / 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 / regulation of peptidyl-tyrosine phosphorylation / 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 / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / negative regulation of neuron differentiation / ECM proteoglycans / intracellular copper ion homeostasis / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / protein serine/threonine kinase binding / positive regulation of chemokine production / clathrin-coated pit / forebrain development / Notch signaling pathway / neuron projection maintenance / positive regulation of protein metabolic process / positive regulation of calcium-mediated signaling / astrocyte activation / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / response to interleukin-1 / cholesterol metabolic process / positive regulation of mitotic cell cycle / extracellular matrix organization / adult locomotory behavior / axonogenesis / platelet alpha granule lumen / trans-Golgi network membrane / positive regulation of peptidyl-threonine phosphorylation / positive regulation of interleukin-1 beta production / learning / dendritic shaft / positive regulation of long-term synaptic potentiation / Mitochondrial protein degradation / central nervous system development / locomotory behavior / endosome lumen / positive regulation of JNK cascade / Post-translational protein phosphorylation / synapse organization / microglial cell activation / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / positive regulation of non-canonical NF-kappaB signal transduction / recycling endosome / cognition / G2/M transition of mitotic cell cycle / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of interleukin-6 production / cellular response to amyloid-beta / endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / serine-type endopeptidase inhibitor activity / positive regulation of peptidyl-serine phosphorylation / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | electron crystallography / cryo EM | |||||||||
Authors | Rodriguez JA / Sawaya MR / Cascio D / Eisenberg DS / Griner SL / Gonen T | |||||||||
Funding support | United States, 1 items
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Citation | Journal: J Biol Chem / Year: 2018 Title: Common fibrillar spines of amyloid-β and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors. Authors: Pascal Krotee / Sarah L Griner / Michael R Sawaya / Duilio Cascio / Jose A Rodriguez / Dan Shi / Stephan Philipp / Kevin Murray / Lorena Saelices / Ji Lee / Paul Seidler / Charles G Glabe / ...Authors: Pascal Krotee / Sarah L Griner / Michael R Sawaya / Duilio Cascio / Jose A Rodriguez / Dan Shi / Stephan Philipp / Kevin Murray / Lorena Saelices / Ji Lee / Paul Seidler / Charles G Glabe / Lin Jiang / Tamir Gonen / David S Eisenberg / Abstract: Amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues and are associated with Alzheimer's disease (AD) and type II diabetes (T2D), ...Amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues and are associated with Alzheimer's disease (AD) and type II diabetes (T2D), respectively. Individuals with T2D have an increased risk of developing AD, and conversely, AD patients have an increased risk of developing T2D. Evidence suggests that this link between AD and T2D might originate from a structural similarity between aggregates of Aβ and hIAPP. Using the cryoEM method microelectron diffraction, we determined the atomic structures of 11-residue segments from both Aβ and hIAPP, termed Aβ(24-34) WT and hIAPP(19-29) S20G, with 64% sequence similarity. We observed a high degree of structural similarity between their backbone atoms (0.96-Å root mean square deviation). Moreover, fibrils of these segments induced amyloid formation through self- and cross-seeding. Furthermore, inhibitors designed for one segment showed cross-efficacy for full-length Aβ and hIAPP and reduced cytotoxicity of both proteins, although by apparently blocking different cytotoxic mechanisms. The similarity of the atomic structures of Aβ(24-34) WT and hIAPP(19-29) S20G offers a molecular model for cross-seeding between Aβ and hIAPP. | |||||||||
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_8720.map.gz | 148.4 KB | EMDB map data format | |
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Header (meta data) | emd-8720-v30.xml emd-8720.xml | 13.2 KB 13.2 KB | Display Display | EMDB header |
Images | emd_8720.png | 288 KB | ||
Filedesc metadata | emd-8720.cif.gz | 5.1 KB | ||
Filedesc structureFactors | emd_8720_sf.cif.gz | 27.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8720 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8720 | HTTPS FTP |
-Validation report
Summary document | emd_8720_validation.pdf.gz | 361.4 KB | Display | EMDB validaton report |
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Full document | emd_8720_full_validation.pdf.gz | 361 KB | Display | |
Data in XML | emd_8720_validation.xml.gz | 4.2 KB | Display | |
Data in CIF | emd_8720_validation.cif.gz | 4.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8720 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8720 | HTTPS FTP |
-Related structure data
Related structure data | 5vosMC 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_8720.map.gz / Format: CCP4 / Size: 211.9 KB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | VGSNKGAIIGL from Amyloid Beta | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X: 0.4675 Å / Y: 0.3916 Å / Z: 0.4648 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 : Fibrils of Amyloid Beta segment 24-34
Entire | Name: Fibrils of Amyloid Beta segment 24-34 |
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Components |
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-Supramolecule #1: Fibrils of Amyloid Beta segment 24-34
Supramolecule | Name: Fibrils of Amyloid Beta segment 24-34 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-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: 1.029213 KDa |
Sequence | String: VGSNKGAIIG L UniProtKB: Amyloid-beta A4 protein |
-Macromolecule #2: water
Macromolecule | Name: water / type: ligand / ID: 2 / Number of copies: 1 / 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 | 7.5 mg/mL | ||||||
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Buffer | pH: 4 / Component:
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Grid | Model: Quantifoil / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE | ||||||
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV | ||||||
Details | nanocrystals | ||||||
Crystal formation | Instrument: microcentrifuge tube / Atmosphere: air / Temperature: 310.0 K / Time: 2.0 DAY / Details: shaking |
-Electron microscopy
Microscope | FEI TECNAI F20 |
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Image recording | Film or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Digitization - Dimensions - Width: 2048 pixel / Digitization - Dimensions - Height: 2048 pixel / Number diffraction images: 471 / Average electron dose: 0.03 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION / Camera length: 1840 mm |
Sample stage | Specimen holder model: GATAN 626 SINGLE TILT LIQUID NITROGEN CRYO TRANSFER HOLDER Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Tecnai F20 / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution method: DIFFRACTION PATTERN/LAYERLINES |
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Molecular replacement | Software - Name: phaser |
Merging software list | Software - Name: XSCALE (ver. Jun 17, 2015) |
Crystallography statistics | Number intensities measured: 5843 / Number structure factors: 1129 / Fourier space coverage: 85.5 / R sym: 0.222 / R merge: 0.222 / Overall phase error: 0 / Overall phase residual: 0.01 / Phase error rejection criteria: 0 / High resolution: 1.42 Å / Shell - Shell ID: 1 / Shell - High resolution: 1.42 Å / Shell - Low resolution: 1.49 Å / Shell - Number structure factors: 84 / Shell - Phase residual: 0.01 / Shell - Fourier space coverage: 47.5 / Shell - Multiplicity: 2.6 |
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: OTHER / Target criteria: Maximum likelihood |
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Output model | PDB-5vos: |