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- EMDB-19129: A DNA Robotic Switch with Regulated Autonomous Display of Cytotox... -
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Open data
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Basic information
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Title | A DNA Robotic Switch with Regulated Autonomous Display of Cytotoxic Ligand Nanopatterns | |||||||||||||||||||||
![]() | From cryoSPARC 3DFlex reconstruct job | |||||||||||||||||||||
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![]() | DNA / DNA origami / Lgand nanopattern / pH sensitive switch / Solid tumor / Death receptor clustering | |||||||||||||||||||||
Biological species | synthetic construct (others) / ![]() | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.4 Å | |||||||||||||||||||||
![]() | Wang Y / Berzina I / Hogberg B | |||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() 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 |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 117.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.9 KB 16.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.6 KB | Display | ![]() |
Images | ![]() | 62 KB | ||
Filedesc metadata | ![]() | 4.5 KB | ||
Others | ![]() ![]() | 14.5 MB 14.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 657.6 KB | Display | ![]() |
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Full document | ![]() | 657.2 KB | Display | |
Data in XML | ![]() | 18.4 KB | Display | |
Data in CIF | ![]() | 24.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | From cryoSPARC 3DFlex reconstruct job | ||||||||||||||||||||
Voxel size | X=Y=Z: 2.2 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: From cryoSPARC 3DFlex reconstruct job
File | emd_19129_half_map_1.map | ||||||||||||
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Annotation | From cryoSPARC 3DFlex reconstruct job | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: From cryoSPARC 3DFlex reconstruct job
File | emd_19129_half_map_2.map | ||||||||||||
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Annotation | From cryoSPARC 3DFlex reconstruct job | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : DNA origami
Entire | Name: DNA origami |
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Components |
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-Supramolecule #1: DNA origami
Supramolecule | Name: DNA origami / type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: synthetic construct (others) |
-Supramolecule #2: ssDNA staples
Supramolecule | Name: ssDNA staples / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: synthetic construct (others) |
-Supramolecule #3: ssDNA scaffold
Supramolecule | Name: ssDNA scaffold / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: ![]() |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 7.4 / Details: 5 mM MgCl2, 5 mM NaCl, 5 mM TRIS, and 1 mM EDTA |
Grid | Model: 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 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 296 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS KRIOS |
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Specialist optics | Phase 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 beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 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 stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |