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Yorodumi- EMDB-23266: Computationally designed octahedral antibody nanocage with Fc o42.1+Fc -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23266 | |||||||||
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Title | Computationally designed octahedral antibody nanocage with Fc o42.1+Fc | |||||||||
Map data | Computationally designed octahedral antibody nanocage with Fc o42.1+Fc | |||||||||
Sample |
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Biological species | synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 11.0 Å | |||||||||
Authors | Dang HV / Veesler D | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Science / Year: 2021 Title: Designed proteins assemble antibodies into modular nanocages. Authors: Robby Divine / Ha V Dang / George Ueda / Jorge A Fallas / Ivan Vulovic / William Sheffler / Shally Saini / Yan Ting Zhao / Infencia Xavier Raj / Peter A Morawski / Madeleine F Jennewein / ...Authors: Robby Divine / Ha V Dang / George Ueda / Jorge A Fallas / Ivan Vulovic / William Sheffler / Shally Saini / Yan Ting Zhao / Infencia Xavier Raj / Peter A Morawski / Madeleine F Jennewein / Leah J Homad / Yu-Hsin Wan / Marti R Tooley / Franziska Seeger / Ali Etemadi / Mitchell L Fahning / James Lazarovits / Alex Roederer / Alexandra C Walls / Lance Stewart / Mohammadali Mazloomi / Neil P King / Daniel J Campbell / Andrew T McGuire / Leonidas Stamatatos / Hannele Ruohola-Baker / Julie Mathieu / David Veesler / David Baker / Abstract: Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by ...Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)-mediated apoptosis, angiopoietin-1 receptor (Tie2)-mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-angiotensin-converting enzyme 2 (ACE2) fusion proteins. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23266.map.gz | 117 MB | EMDB map data format | |
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Header (meta data) | emd-23266-v30.xml emd-23266.xml | 10.3 KB 10.3 KB | Display Display | EMDB header |
Images | emd_23266.png | 59 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23266 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23266 | HTTPS FTP |
-Related structure data
Related structure data | C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23266.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Computationally designed octahedral antibody nanocage with Fc o42.1+Fc | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.16 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Computationally designed octahedral antibody nanocage with Fc o42.1+Fc
Entire | Name: Computationally designed octahedral antibody nanocage with Fc o42.1+Fc |
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Components |
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-Supramolecule #1: Computationally designed octahedral antibody nanocage with Fc o42.1+Fc
Supramolecule | Name: Computationally designed octahedral antibody nanocage with Fc o42.1+Fc type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: synthetic construct (others) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Molecular weight | Theoretical: 1.1 MDa |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.8 mg/mL |
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Buffer | pH: 8 |
Grid | Model: C-flat-1.2/1.3 / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 60.0 e/Å2 |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: cryoSPARC ab initio |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Applied symmetry - Point group: O (octahedral) / Resolution.type: BY AUTHOR / Resolution: 11.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 4032 |