+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-2433 | |||||||||
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Title | Amyloid-beta nanotube | |||||||||
Map data | Reconstruction of an amyloid-beta nanotube | |||||||||
Sample |
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Keywords | nanotube / neurodegeneration / prion-dependent synaptotoxicity | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / negative staining | |||||||||
Authors | Nicoll AJ / Panico S / Freir DB / Wright D / Terry C / Risse E / Herron CE / O'Malley T / Wadsworth JD / Farrow MA ...Nicoll AJ / Panico S / Freir DB / Wright D / Terry C / Risse E / Herron CE / O'Malley T / Wadsworth JD / Farrow MA / Walsh DM / Saibil HR / Collinge J | |||||||||
Citation | Journal: Nat Commun / Year: 2013 Title: Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity. Authors: Andrew J Nicoll / Silvia Panico / Darragh B Freir / Daniel Wright / Cassandra Terry / Emmanuel Risse / Caroline E Herron / Tiernan O'Malley / Jonathan D F Wadsworth / Mark A Farrow / Dominic ...Authors: Andrew J Nicoll / Silvia Panico / Darragh B Freir / Daniel Wright / Cassandra Terry / Emmanuel Risse / Caroline E Herron / Tiernan O'Malley / Jonathan D F Wadsworth / Mark A Farrow / Dominic M Walsh / Helen R Saibil / John Collinge / Abstract: Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-β protein (Aβ) have important roles in Alzheimer's disease with toxicities mimicked by synthetic Aβ(1-42). However, no ...Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-β protein (Aβ) have important roles in Alzheimer's disease with toxicities mimicked by synthetic Aβ(1-42). However, no defined toxic structures acting via specific receptors have been identified and roles of proposed receptors, such as prion protein (PrP), remain controversial. Here we quantify binding to PrP of Aβ(1-42) after different durations of aggregation. We show PrP-binding and PrP-dependent inhibition of long-term potentiation (LTP) correlate with the presence of protofibrils. Globular oligomers bind less avidly to PrP and do not inhibit LTP, whereas fibrils inhibit LTP in a PrP-independent manner. That only certain transient Aβ assemblies cause PrP-dependent toxicity explains conflicting reports regarding the involvement of PrP in Aβ-induced impairments. We show that these protofibrils contain a defined nanotubular structure with a previously unidentified triple helical conformation. Blocking the formation of Aβ nanotubes or their interaction with PrP might have a role in treatment of Alzheimer's disease. | |||||||||
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_2433.map.gz | 241.1 KB | EMDB map data format | |
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Header (meta data) | emd-2433-v30.xml emd-2433.xml | 10.9 KB 10.9 KB | Display Display | EMDB header |
Images | emd_2433.png | 116.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-2433 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-2433 | HTTPS FTP |
-Validation report
Summary document | emd_2433_validation.pdf.gz | 195.2 KB | Display | EMDB validaton report |
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Full document | emd_2433_full_validation.pdf.gz | 194.3 KB | Display | |
Data in XML | emd_2433_validation.xml.gz | 4.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-2433 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-2433 | HTTPS FTP |
-Related structure data
Similar structure data |
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-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_2433.map.gz / Format: CCP4 / Size: 459 KB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Reconstruction of an amyloid-beta nanotube | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 3.26 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 : Amyloid-Beta (1-42) nanotube
Entire | Name: Amyloid-Beta (1-42) nanotube |
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Components |
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-Supramolecule #1000: Amyloid-Beta (1-42) nanotube
Supramolecule | Name: Amyloid-Beta (1-42) nanotube / type: sample / ID: 1000 Details: Protofibrils were prepared from synthetic Amyloid-Beta (1-42) peptide. Briefly hexafluoro-2-propanol-trated Amyloid-beta (1-42) was dissolved in DMSO, diluted into phenol red-free Hams-F12 ...Details: Protofibrils were prepared from synthetic Amyloid-Beta (1-42) peptide. Briefly hexafluoro-2-propanol-trated Amyloid-beta (1-42) was dissolved in DMSO, diluted into phenol red-free Hams-F12 medium, centrifuged and incubated at 22 C for 16 hours. Size of protofibrils ranged from 0.1 to 1 megadaltons Oligomeric state: protofibrils / Number unique components: 1 |
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Molecular weight | Experimental: 500 KDa Method: size-exclusion chromatography with static light scattering |
-Macromolecule #1: Amyloid-beta (1-42)
Macromolecule | Name: Amyloid-beta (1-42) / type: protein_or_peptide / ID: 1 / Recombinant expression: No / Database: NCBI |
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Source (natural) | Organism: Homo sapiens (human) / synonym: human |
-Experimental details
-Structure determination
Method | negative staining |
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Processing | single particle reconstruction |
Aggregation state | filament |
-Sample preparation
Concentration | 0.1 mg/mL |
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Buffer | Details: phenol red-free Ham's F12 cell medium (2% DMSO) |
Staining | Type: NEGATIVE Details: Grids with adsorbed protein were stained with 2% w/v uranyl acetate for 1 minute |
Grid | Details: Negatively glow discharged 300 mesh copper grid with continuous carbon layer |
Vitrification | Cryogen name: NONE / Instrument: OTHER |
-Electron microscopy
Microscope | FEI TECNAI 12 |
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Alignment procedure | Legacy - Astigmatism: corrected for at specimen level |
Date | Jan 10, 2011 |
Image recording | Category: FILM / Film or detector model: KODAK SO-163 FILM / Digitization - Scanner: ZEISS SCAI / Digitization - Sampling interval: 7 µm / Number real images: 50 / Average electron dose: 20 e/Å2 / Bits/pixel: 8 |
Electron beam | Acceleration voltage: 120 kV / Electron source: TUNGSTEN HAIRPIN |
Electron optics | Calibrated magnification: 42986 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.2 mm / Nominal defocus max: 1.0 µm / Nominal defocus min: 0.7 µm / Nominal magnification: 42000 |
Sample stage | Specimen holder model: SIDE ENTRY, EUCENTRIC |
-Image processing
Details | Three-dimensional reconstructions were calculated from extracted, aligned and classified segments and applying helical symmetry, using the pitch independently determined from tomography and single pixel increments in z to generate continuous helices. |
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CTF correction | Details: phase flipping, whole micrograph |
Final reconstruction | Applied symmetry - Helical parameters - Δz: 3.26 Å Applied symmetry - Helical parameters - Δ&Phi: 15 ° Algorithm: OTHER / Software - Name: Spider Details: Maps were calculated from individual classes. Final volume is the average of six maps (maps averaged in CHIMERA). Helical pitch repeat was obtained from tomography data. Since the subunit ...Details: Maps were calculated from individual classes. Final volume is the average of six maps (maps averaged in CHIMERA). Helical pitch repeat was obtained from tomography data. Since the subunit repeat could not be determined, continuous helices were generated. Number images used: 155 |
Final two d classification | Number classes: 6 |