+Open data
-Basic information
Entry | Database: PDB / ID: 7t67 | ||||||
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Title | SARS-CoV-2 S (Spike Glycoprotein) D614G with One(1) RBD Up | ||||||
Components | Spike glycoprotein | ||||||
Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / virus / coronavirus / SARS CoV-2 / SARS-CoV-2 / spike / D614G / RBD / 1 RBD up / one RBD up / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
Authors | Byrne, P.O. / McLellan, J.S. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern. Authors: Matthew R Chang / Luke Tomasovic / Natalia A Kuzmina / Adam J Ronk / Patrick O Byrne / Rebecca Johnson / Nadia Storm / Eduardo Olmedillas / Yixuan J Hou / Alexandra Schäfer / Sarah R Leist ...Authors: Matthew R Chang / Luke Tomasovic / Natalia A Kuzmina / Adam J Ronk / Patrick O Byrne / Rebecca Johnson / Nadia Storm / Eduardo Olmedillas / Yixuan J Hou / Alexandra Schäfer / Sarah R Leist / Longping V Tse / Hanzhong Ke / Christian Coherd / Katrina Nguyen / Maliwan Kamkaew / Anna Honko / Quan Zhu / Galit Alter / Erica Ollmann Saphire / Jason S McLellan / Anthony Griffiths / Ralph S Baric / Alexander Bukreyev / Wayne A Marasco / Abstract: Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being ...Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7t67.cif.gz | 544.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7t67.ent.gz | 451.6 KB | Display | PDB format |
PDBx/mmJSON format | 7t67.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7t67_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7t67_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7t67_validation.xml.gz | 98.1 KB | Display | |
Data in CIF | 7t67_validation.cif.gz | 146.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t6/7t67 ftp://data.pdbj.org/pub/pdb/validation_reports/t6/7t67 | HTTPS FTP |
-Related structure data
Related structure data | 25711MC 7t3mC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 127002.930 Da / Num. of mol.: 3 / Mutation: D614G, R682G, R683S, R685S, K986P, V986P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P0DTC2 #2: Polysaccharide | Source method: isolated from a genetically manipulated source #3: Sugar | ChemComp-NAG / Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Complex of SARS CoV-2 S, Spike Glycoprotein, variant D614G with Antibody 2-7 scFv Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 | ||||||||||||
Source (recombinant) | Organism: Cricetulus griseus (Chinese hamster) | ||||||||||||
Buffer solution | pH: 8 | ||||||||||||
Buffer component |
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Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 41384 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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