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Yorodumi- EMDB-12696: Amyloid beta oligomer displayed on the alpha hemolysin scaffold -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-12696 | |||||||||
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Title | Amyloid beta oligomer displayed on the alpha hemolysin scaffold | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Amyloid beta oligomer / alpha hemolysin / Alzheimer's Disease / TOXIN | |||||||||
Function / homology | Function and homology information cytolysis in another organism / NMDA selective glutamate receptor signaling pathway / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands ...cytolysis in another organism / NMDA selective glutamate receptor signaling pathway / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / axo-dendritic transport / 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 / Lysosome Vesicle Biogenesis / ciliary rootlet / PTB domain binding / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / Golgi-associated vesicle / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / COPII-coated ER to Golgi transport vesicle / suckling behavior / nuclear envelope lumen / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / The NLRP3 inflammasome / neuromuscular process controlling balance / Advanced glycosylation endproduct receptor signaling / transition metal ion binding / regulation of presynapse assembly / negative regulation of long-term synaptic potentiation / negative regulation of neuron differentiation / regulation of multicellular organism growth / intracellular copper ion homeostasis / ECM proteoglycans / trans-Golgi network membrane / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / clathrin-coated pit / protein serine/threonine kinase binding / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / 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 / cholesterol metabolic process / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / response to interleukin-1 / positive regulation of glycolytic process / axonogenesis / positive regulation of mitotic cell cycle / extracellular matrix organization / adult locomotory behavior / platelet alpha granule lumen / positive regulation of interleukin-1 beta production / learning / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / positive regulation of long-term synaptic potentiation / cognition / central nervous system development / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / regulation of long-term neuronal synaptic plasticity / synapse organization / serine-type endopeptidase inhibitor activity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / recycling endosome / positive regulation of interleukin-6 production / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / 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 / neuron projection development / cell-cell junction / Platelet degranulation / synaptic vesicle Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Staphylococcus aureus (bacteria) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Wu J / Blum TB | |||||||||
Citation | Journal: Angew Chem Int Ed Engl / Year: 2021 Title: Cryo-electron Microscopy Imaging of Alzheimer's Amyloid-beta 42 Oligomer Displayed on a Functionally and Structurally Relevant Scaffold. Authors: Jinming Wu / Thorsten B Blum / Daniel P Farrell / Frank DiMaio / Jan Pieter Abrahams / Jinghui Luo / Abstract: Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ oligomers permeabilize cellular membranes, presumably through ...Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ oligomers permeabilize cellular membranes, presumably through a pore formation mechanism. Owing to their structural and stoichiometric heterogeneity, the structure of these pores remains to be characterized. We studied a functional Aβ42-pore equivalent, created by fusing Aβ42 to the oligomerizing, soluble domain of the α-hemolysin (αHL) toxin. Our data reveal Aβ42-αHL oligomers to share major structural, functional, and biological properties with wild-type Aβ42-pores. Single-particle cryo-EM analysis of Aβ42-αHL oligomers (with an overall 3.3 Å resolution) reveals the Aβ42-pore region to be intrinsically flexible. The Aβ42-αHL oligomers will allow many of the features of the wild-type amyloid oligomers to be studied that cannot be otherwise, and may be a highly specific antigen for the development of immuno-base diagnostics and therapies. | |||||||||
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_12696.map.gz | 21.5 MB | EMDB map data format | |
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Header (meta data) | emd-12696-v30.xml emd-12696.xml | 9.3 KB 9.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_12696_fsc.xml | 7.2 KB | Display | FSC data file |
Images | emd_12696.png | 87.1 KB | ||
Filedesc metadata | emd-12696.cif.gz | 5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12696 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12696 | HTTPS FTP |
-Validation report
Summary document | emd_12696_validation.pdf.gz | 405.1 KB | Display | EMDB validaton report |
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Full document | emd_12696_full_validation.pdf.gz | 404.7 KB | Display | |
Data in XML | emd_12696_validation.xml.gz | 9.7 KB | Display | |
Data in CIF | emd_12696_validation.cif.gz | 12.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12696 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12696 | HTTPS FTP |
-Related structure data
Related structure data | 7o1qMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_12696.map.gz / Format: CCP4 / Size: 30.5 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: 1.03 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Abeta42-AHL
Entire | Name: Abeta42-AHL |
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Components |
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-Supramolecule #1: Abeta42-AHL
Supramolecule | Name: Abeta42-AHL / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Alpha-hemolysin hybridized Abeta
Macromolecule | Name: Alpha-hemolysin hybridized Abeta / type: protein_or_peptide / ID: 1 / Number of copies: 7 / Enantiomer: LEVO |
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Source (natural) | Organism: Staphylococcus aureus (bacteria) |
Molecular weight | Theoretical: 33.45927 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: ADSDINIKTG TTDIGSNTTV KTGDLVTYDK ENGMHKKVFY SFIDDKNHNK KLLVIRTKGT IAGQYRVYSE EGANKSGLAW PSAFKVQLQ LPDNEVAQIS DYYPRNDAEF RHDSGYEVHH QKLVFFAEDV GSNKGAIIGL MVGGVVIAYV QPDFKTILES P TDKKVGWK ...String: ADSDINIKTG TTDIGSNTTV KTGDLVTYDK ENGMHKKVFY SFIDDKNHNK KLLVIRTKGT IAGQYRVYSE EGANKSGLAW PSAFKVQLQ LPDNEVAQIS DYYPRNDAEF RHDSGYEVHH QKLVFFAEDV GSNKGAIIGL MVGGVVIAYV QPDFKTILES P TDKKVGWK VIFNNMVNQN WGPYDRDSWN PVYGNQLFMK TRNGSMKAAD NFLDPNKASS LLSSGFSPDF ATVITMDRKA SK QQTNIDV IYERVRDDYQ LHWTSTNWKG TNTKDKWTDR SSERYKIDWE KEEMTN UniProtKB: Alpha-hemolysin, Amyloid-beta precursor protein, Alpha-hemolysin |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.83 mg/mL |
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Buffer | pH: 8 Details: 50 mM Tris-HCl, pH 8.0, 500 mM NaCl, 250 mM imidazole and 0.38 mM DDM |
Grid | Material: GOLD |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |