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Yorodumi- EMDB-58700: Amyloid beta oligomer Interactions with Extracellular Vesicles by... -
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Basic information
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| Title | Amyloid beta oligomer Interactions with Extracellular Vesicles by Cryo-ET | |||||||||
Map data | Small extracellular vesicle with Amyloid beta oligomers 42 | |||||||||
Sample |
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Keywords | Amyloid beta / Small extracellular vesicles / cryo-electron tomography / LIPID BINDING PROTEIN | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | electron tomography / cryo EM / Resolution: 6.7 Å | |||||||||
Authors | Khursheed A / Viles JH / Zhang H / Shang Q / Tian Y / Szwedziak P / Volkov VA | |||||||||
| Funding support | United Kingdom, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2026Title: 3D nanoscale imaging of amyloid-β oligomer interactions with extracellular vesicles by cryo-ET. Authors: Anum Khursheed / Qi Shang / Hui Zhang / Yao Tian / Piotr Szwedziak / Vladimir A Volkov / John H Viles / ![]() Abstract: Central to Alzheimer's disease pathology are prefibrillar oligomer assemblies of amyloid-β (Aβ) peptide. A widely discussed hypothesis proposes that amyloid-β oligomers insert into neuronal lipid ...Central to Alzheimer's disease pathology are prefibrillar oligomer assemblies of amyloid-β (Aβ) peptide. A widely discussed hypothesis proposes that amyloid-β oligomers insert into neuronal lipid membranes, disrupting their integrity and causing a loss of cellular homeostasis in Alzheimer's disease. This membrane disruption is believed to be a major source of Aβ-induced neurotoxicity. Cryo electron tomography (cryo-ET) has facilitated 3D nanoscale imaging of Aβ-membrane interactions under near-native conditions. Analyses of small extracellular vesicles (sEVs) reveals that Aβ oligomers including annular and curvilinear extended oligomers (CLEOs) exhibit extensive binding to cell-derived lipid membranes, including insertion into and carpeting of the lipid bilayer. Notably, these oligomeric assemblies were also internalized and concentrated within the cell-derived exosomes and other small sEVs. Enrichment of Aβ oligomers within the vesicles typically ranged between 5 to 20 times the external Aβ levels depending on the vesicle size and curvature. In contrast, monomeric and fibrillar forms of Aβ displayed minimal membrane interaction. Once internalized CLEOs appear to be trapped in an oligomeric form and do not readily go on to form fibrils. Studies with vesicles of brain lipid extract indicate the Aβ internalization does not require the presence of a membrane protein. Our in vitro studies underscore the membrane-disruptive capacity of oligomeric Aβ species and suggest a role of sEVs in concentrating toxic Aβ oligomers and transporting oligomers across the brain interstitium. | |||||||||
| History |
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_58700.map.gz | 1.6 GB | EMDB map data format | |
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| Header (meta data) | emd-58700-v30.xml emd-58700.xml | 11.2 KB 11.2 KB | Display Display | EMDB header |
| Images | emd_58700.png | 151.1 KB | ||
| Filedesc metadata | emd-58700.cif.gz | 4.1 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-58700 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-58700 | HTTPS FTP |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_58700.map.gz / Format: CCP4 / Size: 1.7 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||
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| Annotation | Small extracellular vesicle with Amyloid beta oligomers 42 | ||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 67 Å | ||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Small extracellular vesicles with Amyloid beta oligomers
| Entire | Name: Small extracellular vesicles with Amyloid beta oligomers |
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| Components |
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-Supramolecule #1: Small extracellular vesicles with Amyloid beta oligomers
| Supramolecule | Name: Small extracellular vesicles with Amyloid beta oligomers type: organelle_or_cellular_component / ID: 1 / Parent: 0 Details: Small extracellular vesicles with Amyloid beta oligomers |
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| Source (natural) | Organism: Homo sapiens (human) / Strain: HEK 293 cell / Organelle: small extracellular vesicles |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | electron tomography |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 / Component - Concentration: 30.0 mM / Component - Formula: HEPES Component - Name: 2-hydroxyethyl)-1-piperazineethanesulfonic acid Details: Sodium phosphate buffer 30 mM and phosphate-buffered saline |
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| Grid | Model: EMS Lacey Carbon / Material: COPPER / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec. / Pretreatment - Atmosphere: OTHER / Pretreatment - Pressure: 0.039 kPa |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 75 % / Chamber temperature: 277.15 K / Instrument: LEICA EM GP |
| Details | small extracellular vesicles incubated with amyloid beta oligomers |
| Sectioning | Other: NO SECTIONING |
| Fiducial marker | Manufacturer: Ted Pella / Diameter: 5 nm |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 0.4 sec. / Average electron dose: 2.92 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 6.0 µm / Nominal defocus min: 3.0 µm / Nominal magnification: 53000 |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
| Final reconstruction | Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 6.7 Å / Software - Name: IMOD / Number images used: 41 |
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| CTF correction | Type: NONE |
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Keywords
Homo sapiens (human)
Authors
United Kingdom, 1 items
Citation

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FIELD EMISSION GUN
