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- EMDB-58700: Amyloid beta oligomer Interactions with Extracellular Vesicles by... -

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Basic information

Entry
Database: EMDB / ID: EMD-58700
TitleAmyloid beta oligomer Interactions with Extracellular Vesicles by Cryo-ET
Map dataSmall extracellular vesicle with Amyloid beta oligomers 42
Sample
  • Organelle or cellular component: Small extracellular vesicles with Amyloid beta oligomers
KeywordsAmyloid beta / Small extracellular vesicles / cryo-electron tomography / LIPID BINDING PROTEIN
Biological speciesHomo sapiens (human)
Methodelectron tomography / cryo EM / Resolution: 6.7 Å
AuthorsKhursheed A / Viles JH / Zhang H / Shang Q / Tian Y / Szwedziak P / Volkov VA
Funding support United Kingdom, 1 items
OrganizationGrant numberCountry
Biotechnology and Biological Sciences Research Council (BBSRC)BB/Y001931/1 United Kingdom
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: 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
DepositionJun 26, 2026-
Header (metadata) releaseJul 8, 2026-
Map releaseJul 8, 2026-
UpdateAug 5, 2026-
Current statusAug 5, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_58700.map.gz / Format: CCP4 / Size: 1.7 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSmall extracellular vesicle with Amyloid beta oligomers 42
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
67 Å/pix.
x 318 pix.
= 21306. Å
67 Å/pix.
x 1440 pix.
= 96480. Å
67 Å/pix.
x 1024 pix.
= 68608. Å

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

generated in cubic-lattice coordinate

Voxel sizeX=Y=Z: 67 Å
Density
Minimum - Maximum-0.2216688 - 0.37345695
Average (Standard dev.)-0.0022366177 (±0.0028788995)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions14401024318
Spacing10241440318
CellA: 68608.0 Å / B: 96480.0 Å / C: 21306.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Small extracellular vesicles with Amyloid beta oligomers

EntireName: Small extracellular vesicles with Amyloid beta oligomers
Components
  • Organelle or cellular component: Small extracellular vesicles with Amyloid beta oligomers

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Supramolecule #1: Small extracellular vesicles with Amyloid beta oligomers

SupramoleculeName: Small extracellular vesicles with Amyloid beta oligomers
type: organelle_or_cellular_component / ID: 1 / Parent: 0
Details: Small extracellular vesicles with Amyloid beta oligomers
Source (natural)Organism: Homo sapiens (human) / Strain: HEK 293 cell / Organelle: small extracellular vesicles

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Experimental details

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Structure determination

Methodcryo EM
Processingelectron tomography
Aggregation stateparticle

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Sample preparation

BufferpH: 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
GridModel: EMS Lacey Carbon / Material: COPPER / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec. / Pretreatment - Atmosphere: OTHER / Pretreatment - Pressure: 0.039 kPa
VitrificationCryogen name: ETHANE / Chamber humidity: 75 % / Chamber temperature: 277.15 K / Instrument: LEICA EM GP
Detailssmall extracellular vesicles incubated with amyloid beta oligomers
SectioningOther: NO SECTIONING
Fiducial markerManufacturer: Ted Pella / Diameter: 5 nm

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average exposure time: 0.4 sec. / Average electron dose: 2.92 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 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 reconstructionAlgorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 6.7 Å / Software - Name: IMOD / Number images used: 41
CTF correctionType: NONE

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