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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-5052 | |||||||||
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Title | cryoEM structure of Abeta(1-42) amyloid fibrils | |||||||||
![]() | This is a cryoEM map of a segment of Abeta(1-42) amyloid fibrils. | |||||||||
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![]() | Alzheimer's disease / amyloid fibrils / Abeta(1-42) / neurodegenerative disease / IHRSR | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 10.0 Å | |||||||||
![]() | Zhang R / Hu X / Khant H / Ludtke SJ / Chiu W / Schmid MF / Frieden C / Lee J-M | |||||||||
![]() | ![]() Title: Interprotofilament interactions between Alzheimer's Abeta1-42 peptides in amyloid fibrils revealed by cryoEM. Authors: Rui Zhang / Xiaoyan Hu / Htet Khant / Steven J Ludtke / Wah Chiu / Michael F Schmid / Carl Frieden / Jin-Moo Lee / ![]() Abstract: Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. This amyloid primarily contains amyloid-beta (Abeta), a 39- to 43-aa peptide ...Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. This amyloid primarily contains amyloid-beta (Abeta), a 39- to 43-aa peptide derived from the proteolytic cleavage of the endogenous amyloid precursor protein. The 42-residue-length Abeta peptide (Abeta(1-42)), the most abundant Abeta peptide found in plaques, has a much greater propensity to self-aggregate into fibrils than the other peptides and is believed to be more pathogenic. Synthetic human Abeta(1-42) peptides self-aggregate into stable but poorly-ordered helical filaments. We determined their structure to approximately 10-A resolution by using cryoEM and the iterative real-space reconstruction method. This structure reveals 2 protofilaments winding around a hollow core. Previous hairpin-like NMR models for Abeta(17-42) fit well in the cryoEM density map and reveal that the juxtaposed protofilaments are joined via the N terminus of the peptide from 1 protofilament connecting to the loop region of the peptide in the opposite protofilament. This model of mature Abeta(1-42) fibrils is markedly different from previous cryoEM models of Abeta(1-40) fibrils. In our model, the C terminus of Abeta forms the inside wall of the hollow core, which is supported by partial proteolysis analysis. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 4.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11 KB 11 KB | Display Display | ![]() |
Images | ![]() | 56 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Similar structure data |
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Links
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Related items in Molecule of the Month |
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Map
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Annotation | This is a cryoEM map of a segment of Abeta(1-42) amyloid fibrils. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.81 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Abeta(1-42) amyloid fibril
Entire | Name: Abeta(1-42) amyloid fibril |
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Components |
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-Supramolecule #1000: Abeta(1-42) amyloid fibril
Supramolecule | Name: Abeta(1-42) amyloid fibril / type: sample / ID: 1000 Details: The sample was prepared in 10mM HCl buffer for 1 month to form fibrils. Number unique components: 1 |
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-Macromolecule #1: Abeta(1-42) amyloid fibril
Macromolecule | Name: Abeta(1-42) amyloid fibril / type: protein_or_peptide / ID: 1 / Name.synonym: Abeta(1-42) amyloid fibril Details: The component of this amyloid fibril is a 42-residue peptide. Dry synthetic human Abeta1-42 peptides were purchased from American Peptide Company Inc. Oligomeric state: helical / Recombinant expression: No / Database: NCBI |
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Molecular weight | Experimental: 5 KDa / Theoretical: 5 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Concentration | 0.9 mg/mL |
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Buffer | pH: 2 / Details: 10mM HCl, 2% DMSO |
Grid | Details: Quantifoil 200 mesh grid |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 90 K / Instrument: OTHER / Details: Vitrification instrument: vitrobot / Method: 2 blots, each 2 seconds before plunging |
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Electron microscopy
Microscope | JEOL 2010F |
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Temperature | Min: 93 K / Max: 93 K / Average: 93 K |
Alignment procedure | Legacy - Astigmatism: objective lens astigmatism was corrected at 400,000 times magnification |
Specialist optics | Energy filter - Name: JEOL |
Date | Dec 9, 2006 |
Image recording | Category: CCD / Film or detector model: GENERIC GATAN / Number real images: 208 / Average electron dose: 18 e/Å2 / Bits/pixel: 8 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2 mm / Nominal defocus max: 3.4 µm / Nominal defocus min: 1.8 µm / Nominal magnification: 60000 |
Sample stage | Specimen holder: Eucentric / Specimen holder model: GATAN LIQUID NITROGEN |
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Image processing
Details | The long straight filaments were boxed out from the raw electron micrograph using EMAN helixboxer program. |
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Final reconstruction | Applied symmetry - Helical parameters - Axial symmetry: C2 (2 fold cyclic) Algorithm: OTHER / Resolution.type: BY AUTHOR / Resolution: 10.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: IHRSR Details: We sorted heterogeneous dataset into homogeneous subgroups. And the deposited map is the reconstruction for one of the subgroups . |
CTF correction | Details: each micrograph by binnary phase flipping |
-Atomic model buiding 1
Initial model | PDB ID: Chain - Chain ID: A |
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Details | PDBEntryID_givenInChain. Protocol: manually fit. manually fit 10 abeta(1-42) monomers into one strand of cryoEM map. |
Refinement | Space: REAL / Protocol: RIGID BODY FIT |