+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 regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / smooth endoplasmic reticulum calcium ion homeostasis ...regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / smooth endoplasmic reticulum calcium ion homeostasis / axon midline choice point recognition / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / regulation of Wnt signaling pathway / mating behavior / positive regulation of amyloid fibril formation / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / : / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / presynaptic active zone / nuclear envelope lumen / modulation of excitatory postsynaptic potential / suckling behavior / COPII-coated ER to Golgi transport vesicle / dendrite development / smooth endoplasmic reticulum / regulation of NMDA receptor activity / TRAF6 mediated NF-kB activation / negative regulation of long-term synaptic potentiation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / regulation of presynapse assembly / The NLRP3 inflammasome / intracellular copper ion homeostasis / transition metal ion binding / regulation of multicellular organism growth / negative regulation of neuron differentiation / ECM proteoglycans / spindle midzone / positive regulation of T cell migration / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / forebrain development / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / clathrin-coated pit / Notch signaling pathway / cholesterol metabolic process / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / neuron projection maintenance / positive regulation of glycolytic process / extracellular matrix organization / positive regulation of mitotic cell cycle / response to interleukin-1 / axonogenesis / adult locomotory behavior / trans-Golgi network membrane / dendritic shaft / locomotory behavior / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation / learning / positive regulation of interleukin-1 beta production / central nervous system development / positive regulation of long-term synaptic potentiation / astrocyte activation / endosome lumen / Post-translational protein phosphorylation / synapse organization / microglial cell activation / regulation of long-term neuronal synaptic plasticity / positive regulation of JNK cascade / TAK1-dependent IKK and NF-kappa-B activation / neuromuscular junction / visual learning / serine-type endopeptidase inhibitor activity / recycling endosome / cognition / positive regulation of inflammatory response / positive regulation of interleukin-6 production / neuron cellular homeostasis / Golgi lumen / endocytosis / positive regulation of non-canonical NF-kappaB signal transduction / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / neuron projection development / cellular response to amyloid-beta / positive regulation of DNA-binding transcription factor activity / G2/M transition of mitotic cell cycle / cell-cell junction / synaptic vesicle / positive regulation of tumor necrosis factor production / regulation of translation 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_unfiltered_unmasked.map | 15.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-3132 ftp://ftp.pdbj.org/pub/emdb/structures/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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 unfiltered unmasked.map
File | EMD_3132_unfiltered_unmasked.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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 58333 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / 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 |
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 |
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |