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- EMDB-19129: A DNA Robotic Switch with Regulated Autonomous Display of Cytotox... -

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Basic information

Entry
Database: EMDB / ID: EMD-19129
TitleA DNA Robotic Switch with Regulated Autonomous Display of Cytotoxic Ligand Nanopatterns
Map dataFrom cryoSPARC 3DFlex reconstruct job
Sample
  • Complex: DNA origami
    • Complex: ssDNA staples
    • Complex: ssDNA scaffold
KeywordsDNA / DNA origami / Lgand nanopattern / pH sensitive switch / Solid tumor / Death receptor clustering
Biological speciessynthetic construct (others) / Phage M13mp18 (virus)
Methodsingle particle reconstruction / cryo EM / Resolution: 7.4 Å
AuthorsWang Y / Berzina I / Hogberg B
Funding support Sweden, European Union, Finland, 6 items
OrganizationGrant numberCountry
Knut and Alice Wallenberg FoundationKAW 2017.0114 Sweden
Knut and Alice Wallenberg FoundationKAW 2017.0276) Sweden
European Research Council (ERC)Cell Track GA No. 724872European Union
Swedish Research Council2019-01474 Sweden
Swedish Research Council2023-00289 Sweden
Academy of Finland341908 Finland
CitationJournal: Nat Nanotechnol / Year: 2024
Title: A DNA robotic switch with regulated autonomous display of cytotoxic ligand nanopatterns.
Authors: Yang Wang / Igor Baars / Ieva Berzina / Iris Rocamonde-Lago / Boxuan Shen / Yunshi Yang / Marco Lolaico / Janine Waldvogel / Ioanna Smyrlaki / Keying Zhu / Robert A Harris / Björn Högberg /
Abstract: The clustering of death receptors (DRs) at the membrane leads to apoptosis. With the goal of treating tumours, multivalent molecular tools that initiate this mechanism have been developed. However, ...The clustering of death receptors (DRs) at the membrane leads to apoptosis. With the goal of treating tumours, multivalent molecular tools that initiate this mechanism have been developed. However, DRs are also ubiquitously expressed in healthy tissue. Here we present a stimuli-responsive robotic switch nanodevice that can autonomously and selectively turn on the display of cytotoxic ligand patterns in tumour microenvironments. We demonstrate a switchable DNA origami that normally hides six ligands but displays them as a hexagonal pattern 10 nm in diameter once under higher acidity. This can effectively cluster DRs and trigger apoptosis of human breast cancer cells at pH 6.5 while remaining inert at pH 7.4. When administered to mice bearing human breast cancer xenografts, this nanodevice decreased tumour growth by up to 70%. The data demonstrate the feasibility and opportunities for developing ligand pattern switches as a path for targeted treatment.
History
DepositionDec 13, 2023-
Header (metadata) releaseJul 10, 2024-
Map releaseJul 10, 2024-
UpdateOct 2, 2024-
Current statusOct 2, 2024Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_19129.png

Downloads & links

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Map

FileDownload / File: emd_19129.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationFrom cryoSPARC 3DFlex reconstruct job
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.2 Å/pix.
x 320 pix.
= 704. Å		2.2 Å/pix.
x 320 pix.
= 704. Å		2.2 Å/pix.
x 320 pix.
= 704. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.2 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.014
Minimum - Maximum-0.023316177 - 0.07724496
Average (Standard dev.)0.0013319443 (±0.0054964432)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 704.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: From cryoSPARC 3DFlex reconstruct job

Fileemd_19129_half_map_1.map
AnnotationFrom cryoSPARC 3DFlex reconstruct job
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: From cryoSPARC 3DFlex reconstruct job

Fileemd_19129_half_map_2.map
AnnotationFrom cryoSPARC 3DFlex reconstruct job
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : DNA origami

EntireName: DNA origami
Components
  • Complex: DNA origami
    • Complex: ssDNA staples
    • Complex: ssDNA scaffold

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Supramolecule #1: DNA origami

SupramoleculeName: DNA origami / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: synthetic construct (others)

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Supramolecule #2: ssDNA staples

SupramoleculeName: ssDNA staples / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: synthetic construct (others)

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Supramolecule #3: ssDNA scaffold

SupramoleculeName: ssDNA scaffold / type: complex / ID: 3 / Parent: 1
Source (natural)Organism: Phage M13mp18 (virus)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1 mg/mL
BufferpH: 7.4 / Details: 5 mM MgCl2, 5 mM NaCl, 5 mM TRIS, and 1 mM EDTA
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 3 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 296 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsPhase plate: VOLTA PHASE PLATE / Energy filter - Slit width: 10 eV
Image recording#0 - Image recording ID: 1 / #0 - Film or detector model: GATAN K3 (6k x 4k) / #0 - Number grids imaged: 1 / #0 - Number real images: 6652 / #0 - Average exposure time: 4.4 sec. / #0 - Average electron dose: 40.0 e/Å2 / #1 - Image recording ID: 2 / #1 - Film or detector model: GATAN K3 (6k x 4k) / #1 - Number grids imaged: 1 / #1 - Number real images: 5195 / #1 - Average exposure time: 6.0 sec. / #1 - Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 81000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Image recording ID1
Startup modelType of model: OTHER / Details: Ab initio map
Final reconstructionResolution.type: BY AUTHOR / Resolution: 7.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 88000
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
FSC plot (resolution estimation)

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