+Open data
-Basic information
Entry | Database: PDB / ID: 8gjn | ||||||
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Title | 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer | ||||||
Components |
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Keywords | VIRAL PROTEIN | ||||||
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 / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / 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 | Mus musculus (house mouse) Severe acute respiratory syndrome coronavirus 2 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
Authors | Kwon, H.J. / Zhang, J. / Kosikova, M. / Tang, W.C. / Rodriguez, U.O. / Peng, H.Q. / Meseda, C.A. / Pedro, C.L. / Schmeisser, F. / Lu, J.M. ...Kwon, H.J. / Zhang, J. / Kosikova, M. / Tang, W.C. / Rodriguez, U.O. / Peng, H.Q. / Meseda, C.A. / Pedro, C.L. / Schmeisser, F. / Lu, J.M. / Zhou, B. / Davis, C.T. / Wentworth, D.E. / Chen, W.H. / Shriver, M.C. / Pasetti, M.F. / Weir, J.P. / Chen, B. / Xie, H. | ||||||
Funding support | United States, 1items
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Citation | Journal: J Med Virol / Year: 2023 Title: Distinct in vitro and in vivo neutralization profiles of monoclonal antibodies elicited by the receptor binding domain of the ancestral SARS-CoV-2. Authors: Hyung J Kwon / Jun Zhang / Matina Kosikova / Weichun Tang / Uriel Ortega-Rodriguez / Hanqin Peng / Clement A Meseda / Cyntia L Pedro / Falko Schmeisser / Jianming Lu / Insung Kang / Bin Zhou ...Authors: Hyung J Kwon / Jun Zhang / Matina Kosikova / Weichun Tang / Uriel Ortega-Rodriguez / Hanqin Peng / Clement A Meseda / Cyntia L Pedro / Falko Schmeisser / Jianming Lu / Insung Kang / Bin Zhou / Charles T Davis / David E Wentworth / Wilbur H Chen / Mallory C Shriver / Robin S Barnes / Marcela F Pasetti / Jerry P Weir / Bing Chen / Hang Xie / Abstract: Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are sought to curb coronavirus disease 2019 (COVID-19) infections. Here we produced and ...Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are sought to curb coronavirus disease 2019 (COVID-19) infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS-CoV-2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC ) ≤135 ng/mL against infectious SARS-CoV-2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5, and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18-hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma, and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif in the RBD-up conformation. A third RBD-reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross-neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID-19 convalescent sera or postvaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS-CoV-2 variants and elicited antibody responses. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8gjn.cif.gz | 85.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8gjn.ent.gz | 64.6 KB | Display | PDB format |
PDBx/mmJSON format | 8gjn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8gjn_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8gjn_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8gjn_validation.xml.gz | 30.7 KB | Display | |
Data in CIF | 8gjn_validation.cif.gz | 40.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gj/8gjn ftp://data.pdbj.org/pub/pdb/validation_reports/gj/8gjn | HTTPS FTP |
-Related structure data
Related structure data | 40095MC 8gjmC M: map data used to model this data C: citing same article (ref.) |
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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: Antibody | Mass: 15353.094 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 14090.899 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) |
#3: Protein | Mass: 22218.936 Da / Num. of mol.: 1 / Fragment: RBD Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
#4: Sugar | ChemComp-NAG / |
Has ligand of interest | Y |
-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: 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer Type: COMPLEX Details: 17B10 fab in complex with up-RBD of SARS-CoV-2 Spike G614 trimer Entity ID: #1-#3 / Source: MULTIPLE SOURCES | ||||||||||||||||||||
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Molecular weight | Value: 0.1 MDa / Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 | ||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
-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: 2200 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 54.442 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 3124974 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 439265 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 7KRR Pdb chain-ID: A / Accession code: 7KRR / Chain residue range: 14-1211 / Pdb chain residue range: 14-1211 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
Refine LS restraints |
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