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- EMDB-21501: Amyloid-beta(1-40) fibril derived from Alzheimer's disease cortic... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21501 | |||||||||
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Title | Amyloid-beta(1-40) fibril derived from Alzheimer's disease cortical tissue | |||||||||
![]() | CryoEM density map from RELION-based analysis | |||||||||
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Function / homology | ![]() 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 / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | helical reconstruction / ![]() | |||||||||
![]() | Ghosh U / Thurber KR | |||||||||
![]() | ![]() Title: Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue. Authors: Ujjayini Ghosh / Kent R Thurber / Wai-Ming Yau / Robert Tycko / ![]() Abstract: Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer's disease (AD). We report ...Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer's disease (AD). We report the molecular structure of a specific fibril polymorph, formed by 40-residue Aβ peptides (Aβ40), that is derived from cortical tissue of an AD patient by seeded fibril growth. The structure is determined from cryogenic electron microscopy (cryoEM) images, supplemented by mass-per-length (MPL) measurements and solid-state NMR (ssNMR) data. Previous ssNMR studies with multiple AD patients had identified this polymorph as the most prevalent brain-derived Aβ40 fibril polymorph from typical AD patients. The structure, which has 2.8-Å resolution according to standard criteria, differs qualitatively from all previously described Aβ fibril structures, both in its molecular conformations and its organization of cross-β subunits. Unique features include twofold screw symmetry about the fibril growth axis, despite an MPL value that indicates three Aβ40 molecules per 4.8-Å β-sheet spacing, a four-layered architecture, and fully extended conformations for molecules in the central two cross-β layers. The cryoEM density, ssNMR data, and MPL data are consistent with β-hairpin conformations for molecules in the outer cross-β layers. Knowledge of this brain-derived fibril structure may contribute to the development of structure-specific amyloid imaging agents and aggregation inhibitors with greater diagnostic and therapeutic utility. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 224.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.3 KB 14.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.1 KB | Display | ![]() |
Images | ![]() | 120.4 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Filedesc metadata | ![]() | 6.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6w0oMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | CryoEM density map from RELION-based analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : amyloid-beta(1-40) fibrils derived from human AD brain
Entire | Name: amyloid-beta(1-40) fibrils derived from human AD brain |
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Components |
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-Supramolecule #1: amyloid-beta(1-40) fibrils derived from human AD brain
Supramolecule | Name: amyloid-beta(1-40) fibrils derived from human AD brain type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Fibrils produced by seeded growth using amyloid-beta in brain extract as the source of seeds. CryoEM and solid state NMR measurements were performed on second-generation seeded fibrils. |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 29 kDa/nm |
-Macromolecule #1: Amyloid-beta precursor protein
Macromolecule | Name: Amyloid-beta precursor protein / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 4.335852 KDa |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV UniProtKB: ![]() |
-Experimental details
-Structure determination
Method | ![]() |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Concentration | 0.45 mg/mL |
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Buffer | pH: 7.4 / Component - Concentration: 10.0 mM / Component - Formula: Na2HPO4/NaH2PO4 / Component - Name: Phosphate buffer Details: 10 mM phosphate buffer with 0.01% NaN3 to avoid microbial contamination. Buffers were filtered to avoid contamination. |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: OTHER / Pretreatment - Pressure: 0.036000000000000004 kPa / Details: The grids were checked in microscope prior to use. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 293 K / Instrument: LEICA PLUNGER Details: The grids were preblotted for 10 seconds and blotted for 6 seconds before plunging.. |
Details | Protein exists in solution as amyloid fibrils of varying lengths. |
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Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Alignment procedure | Coma free - Residual tilt: 6.0 mrad |
Details | Preliminary grid screening was done manually in FEI T12. |
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 1337 / Average exposure time: 10.0 sec. / Average electron dose: 73.5 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Details | Xplor-NIH was used to combine EM density with phi/psi restraints from NMR chemical shifts (from Talos-N Version 4.21 Rev 2016.343.11.31). |
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Refinement | Space: REAL / Protocol: AB INITIO MODEL |
Output model | ![]() PDB-6w0o: |