+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-3132 | |||||||||
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Title | Electron cryo-microscopy of an Abeta(1-42)amyloid fibril | |||||||||
Map data | Reconstruction of an Abeta(1-42) amyloid-like fibril | |||||||||
Sample |
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Keywords | Alzheimer's disease / Abeta(1-42) / amyloid fibril / protein aggregation / protein folding / cross-beta / Frealix | |||||||||
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 | helical reconstruction / cryo EM / Resolution: 7.0 Å | |||||||||
Authors | Schmidt M / Rohou A / Lasker K / Yadav J-K / Schiene-Fischer C / Fandrich M / Grigorieff N | |||||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2015 Title: Peptide dimer structure in an Aβ(1-42) fibril visualized with cryo-EM. Authors: Matthias Schmidt / Alexis Rohou / Keren Lasker / Jay K Yadav / Cordelia Schiene-Fischer / Marcus Fändrich / Nikolaus Grigorieff / Abstract: Alzheimer's disease (AD) is a fatal neurodegenerative disorder in humans and the main cause of dementia in aging societies. The disease is characterized by the aberrant formation of β-amyloid (Aβ) ...Alzheimer's disease (AD) is a fatal neurodegenerative disorder in humans and the main cause of dementia in aging societies. The disease is characterized by the aberrant formation of β-amyloid (Aβ) peptide oligomers and fibrils. These structures may damage the brain and give rise to cerebral amyloid angiopathy, neuronal dysfunction, and cellular toxicity. Although the connection between AD and Aβ fibrillation is extensively documented, much is still unknown about the formation of these Aβ aggregates and their structures at the molecular level. Here, we combined electron cryomicroscopy, 3D reconstruction, and integrative structural modeling methods to determine the molecular architecture of a fibril formed by Aβ(1-42), a particularly pathogenic variant of Aβ peptide. Our model reveals that the individual layers of the Aβ fibril are formed by peptide dimers with face-to-face packing. The two peptides forming the dimer possess identical tilde-shaped conformations and interact with each other by packing of their hydrophobic C-terminal β-strands. The peptide C termini are located close to the main fibril axis, where they produce a hydrophobic core and are surrounded by the structurally more flexible and charged segments of the peptide N termini. The observed molecular architecture is compatible with the general chemical properties of Aβ peptide and provides a structural basis for various biological observations that illuminate the molecular underpinnings of AD. Moreover, the structure provides direct evidence for a steric zipper within a fibril formed by full-length Aβ peptide. | |||||||||
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_3132.map.gz | 12.4 MB | EMDB map data format | |
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Header (meta data) | emd-3132-v30.xml emd-3132.xml | 10.5 KB 10.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_3132_fsc.xml | 5.9 KB | Display | FSC data file |
Images | emd_3132.png | 413.9 KB | ||
Others | emd_3132_additional_1.map.gz | 14.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-3132 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3132 | HTTPS FTP |
-Validation report
Summary document | emd_3132_validation.pdf.gz | 215.3 KB | Display | EMDB validaton report |
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Full document | emd_3132_full_validation.pdf.gz | 214.4 KB | Display | |
Data in XML | emd_3132_validation.xml.gz | 7.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3132 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3132 | HTTPS FTP |
-Related structure data
Related structure data | 5aefMC 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_3132.map.gz / Format: CCP4 / Size: 14.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Reconstruction of an Abeta(1-42) amyloid-like fibril | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Supplemental map: emd 3132 additional 1.map
File | emd_3132_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Abeta(1-42) amyloid-like fibril
Entire | Name: Abeta(1-42) amyloid-like fibril |
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Components |
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-Supramolecule #1000: Abeta(1-42) amyloid-like fibril
Supramolecule | Name: Abeta(1-42) amyloid-like fibril / type: sample / ID: 1000 / Details: fibril / Oligomeric state: Peptide forms a helical assembly / Number unique components: 1 |
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-Macromolecule #1: Abeta(1-42)
Macromolecule | Name: Abeta(1-42) / type: protein_or_peptide / ID: 1 / Oligomeric state: Multimer / Recombinant expression: No / Database: NCBI |
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Source (natural) | Organism: Homo sapiens (human) / synonym: Human / Tissue: Brain |
Molecular weight | Experimental: 4.418 KDa / Theoretical: 4.418 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 7.4 / Details: 50mM Tris-HCl |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 40 % / Chamber temperature: 100 K / Instrument: GATAN CRYOPLUNGE 3 Method: grids: glow-discharged holey-carbon Blotting: 4 second backside blotting |
-Electron microscopy
Microscope | FEI TECNAI F30 |
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Temperature | Average: 100 K |
Date | Feb 5, 2010 |
Image recording | Category: FILM / Film or detector model: KODAK SO-163 FILM / Digitization - Scanner: ZEISS SCAI / Digitization - Sampling interval: 7 µm / Number real images: 29 / Average electron dose: 30 e/Å2 / Bits/pixel: 14 |
Tilt angle min | 0 |
Tilt angle max | 0 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 58333 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.0 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.75 µm / Nominal magnification: 59000 |
Sample stage | Specimen holder model: GATAN LIQUID NITROGEN |
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |