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Yorodumi- EMDB-3851: Near-atomic resolution fibril structure of complete amyloid-beta(... -
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-Basic information
Entry | Database: EMDB / ID: EMD-3851 | |||||||||
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Title | Near-atomic resolution fibril structure of complete amyloid-beta(1-42) by cryo-EM | |||||||||
Map data | The density map was sharpened by a B-factor of -50 Ang^2 and filtered to 3.5 Ang. This density map was used for model building and refinement. | |||||||||
Sample |
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Keywords | amyloid / fibril / aggregation / Alzheimer's disease / 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 | helical reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
Authors | Gremer L / Schoelzel D | |||||||||
Citation | Journal: Science / Year: 2017 Title: Fibril structure of amyloid-β(1-42) by cryo-electron microscopy. Authors: Lothar Gremer / Daniel Schölzel / Carla Schenk / Elke Reinartz / Jörg Labahn / Raimond B G Ravelli / Markus Tusche / Carmen Lopez-Iglesias / Wolfgang Hoyer / Henrike Heise / Dieter ...Authors: Lothar Gremer / Daniel Schölzel / Carla Schenk / Elke Reinartz / Jörg Labahn / Raimond B G Ravelli / Markus Tusche / Carmen Lopez-Iglesias / Wolfgang Hoyer / Henrike Heise / Dieter Willbold / Gunnar F Schröder / Abstract: Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease ...Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease patients. We present the structure of an Aβ(1-42) fibril composed of two intertwined protofilaments determined by cryo-electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall "LS"-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed "groove" and "ridge," leading to different binding pathways on both fibril ends, which has implications for fibril growth. | |||||||||
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_3851.map.gz | 36.1 MB | EMDB map data format | |
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Header (meta data) | emd-3851-v30.xml emd-3851.xml | 15.9 KB 15.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_3851_fsc.xml | 7.7 KB | Display | FSC data file |
Images | emd_3851.png | 147.8 KB | ||
Filedesc metadata | emd-3851.cif.gz | 5.5 KB | ||
Others | emd_3851_half_map_1.map.gz emd_3851_half_map_2.map.gz | 13.5 MB 13.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-3851 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3851 | HTTPS FTP |
-Validation report
Summary document | emd_3851_validation.pdf.gz | 385 KB | Display | EMDB validaton report |
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Full document | emd_3851_full_validation.pdf.gz | 384.1 KB | Display | |
Data in XML | emd_3851_validation.xml.gz | 13.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3851 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3851 | HTTPS FTP |
-Related structure data
Related structure data | 5oqvMC 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_3851.map.gz / Format: CCP4 / Size: 38.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | The density map was sharpened by a B-factor of -50 Ang^2 and filtered to 3.5 Ang. This density map was used for model building and refinement. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.935 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: even half map.
File | emd_3851_half_map_1.map | ||||||||||||
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Annotation | even half map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: odd half map.
File | emd_3851_half_map_2.map | ||||||||||||
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Annotation | odd half map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Beta-amyloid protein 42 fibrils
Entire | Name: Beta-amyloid protein 42 fibrils |
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Components |
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-Supramolecule #1: Beta-amyloid protein 42 fibrils
Supramolecule | Name: Beta-amyloid protein 42 fibrils / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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: 9 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 4.520087 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IA UniProtKB: Amyloid-beta precursor protein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 2 Component:
Details: in water | ||||||
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Grid | Model: UltrAuFoil R 1.2/1.3 Quantifoil / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE | ||||||
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV Details: 2.5 microL sample was applied to the grid, blotted for 2.5 s before plunging.. |
-Electron microscopy
Microscope | FEI TECNAI ARCTICA |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: INTEGRATING / Number grids imaged: 1 / Number real images: 2026 / Average exposure time: 2.0 sec. / Average electron dose: 24.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 110000 |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL / Target criteria: Cross-correlation coefficient |
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Output model | PDB-5oqv: |