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Yorodumi- PDB-7jmw: Crystal structure of SARS-CoV-2 spike protein receptor-binding do... -
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-Basic information
Entry | Database: PDB / ID: 7jmw | |||||||||
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Title | Crystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with cross-neutralizing antibody COVA1-16 Fab | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Antibody / Spike / Coronavirus / COVID-19 / IMMUNE SYSTEM / 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 Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.89 Å | |||||||||
Authors | Liu, H. / Yuan, M. / Zhu, X. / Wu, N.C. / Wilson, I.A. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Immunity / Year: 2020 Title: Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity. Authors: Hejun Liu / Nicholas C Wu / Meng Yuan / Sandhya Bangaru / Jonathan L Torres / Tom G Caniels / Jelle van Schooten / Xueyong Zhu / Chang-Chun D Lee / Philip J M Brouwer / Marit J van Gils / ...Authors: Hejun Liu / Nicholas C Wu / Meng Yuan / Sandhya Bangaru / Jonathan L Torres / Tom G Caniels / Jelle van Schooten / Xueyong Zhu / Chang-Chun D Lee / Philip J M Brouwer / Marit J van Gils / Rogier W Sanders / Andrew B Ward / Ian A Wilson / Abstract: Most antibodies isolated from individuals with coronavirus disease 2019 (COVID-19) are specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, COVA1-16 is a relatively rare ...Most antibodies isolated from individuals with coronavirus disease 2019 (COVID-19) are specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here, we determined a crystal structure of the COVA1-16 antibody fragment (Fab) with the SARS-CoV-2 receptor-binding domain (RBD) and negative-stain electron microscopy reconstructions with the spike glycoprotein trimer to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long complementarity-determining region (CDR) H3, and competes with the angiotensin-converting enzyme 2 (ACE2) receptor because of steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with the structural and functional rationale for epitope conservation, provide insights for development of more universal SARS-like coronavirus vaccines and therapies. #1: Journal: Biorxiv / Year: 2020 Title: Cross-neutralization of a SARS-CoV-2 antibody to a functionally conserved site is mediated by avidity. Authors: Liu, H. / Wu, N.C. / Yuan, M. / Bangaru, S. / Torres, J.L. / Caniels, T.G. / van Schooten, J. / Zhu, X. / Lee, C.D. / Brouwer, P.J.M. / van Gils, M.J. / Sanders, R.W. / Ward, A.B. / Wilson, I.A. #2: Journal: Immunity / Year: 2020 Title: Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity. Authors: Hejun Liu / Nicholas C Wu / Meng Yuan / Sandhya Bangaru / Jonathan L Torres / Tom G Caniels / Jelle van Schooten / Xueyong Zhu / Chang-Chun D Lee / Philip J M Brouwer / Marit J van Gils / ...Authors: Hejun Liu / Nicholas C Wu / Meng Yuan / Sandhya Bangaru / Jonathan L Torres / Tom G Caniels / Jelle van Schooten / Xueyong Zhu / Chang-Chun D Lee / Philip J M Brouwer / Marit J van Gils / Rogier W Sanders / Andrew B Ward / Ian A Wilson / Abstract: Most antibodies isolated from individuals with coronavirus disease 2019 (COVID-19) are specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, COVA1-16 is a relatively rare ...Most antibodies isolated from individuals with coronavirus disease 2019 (COVID-19) are specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here, we determined a crystal structure of the COVA1-16 antibody fragment (Fab) with the SARS-CoV-2 receptor-binding domain (RBD) and negative-stain electron microscopy reconstructions with the spike glycoprotein trimer to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long complementarity-determining region (CDR) H3, and competes with the angiotensin-converting enzyme 2 (ACE2) receptor because of steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with the structural and functional rationale for epitope conservation, provide insights for development of more universal SARS-like coronavirus vaccines and therapies. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7jmw.cif.gz | 305.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7jmw.ent.gz | 206.4 KB | Display | PDB format |
PDBx/mmJSON format | 7jmw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7jmw_validation.pdf.gz | 751.9 KB | Display | wwPDB validaton report |
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Full document | 7jmw_full_validation.pdf.gz | 759.4 KB | Display | |
Data in XML | 7jmw_validation.xml.gz | 23.5 KB | Display | |
Data in CIF | 7jmw_validation.cif.gz | 32 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jm/7jmw ftp://data.pdbj.org/pub/pdb/validation_reports/jm/7jmw | HTTPS FTP |
-Related structure data
Related structure data | 7jmxC 2q20S 4imkS 6xc4S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 26095.348 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P0DTC2 |
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#2: Antibody | Mass: 25928.943 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Mus musculus (house mouse) |
#3: Antibody | Mass: 23415.799 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Mus musculus (house mouse) |
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.72 Å3/Da / Density % sol: 54.82 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop / pH: 6.9 / Details: 20% PEG 3350, 0.2 M Na-iodide, pH 6.9 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-1 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 10, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.89→50 Å / Num. obs: 17656 / % possible obs: 97.9 % / Redundancy: 3.7 % / Biso Wilson estimate: 42.71 Å2 / CC1/2: 0.963 / Rpim(I) all: 0.09 / Rsym value: 0.153 / Net I/σ(I): 7.4 |
Reflection shell | Resolution: 2.89→2.95 Å / Mean I/σ(I) obs: 1.2 / Num. unique obs: 845 / CC1/2: 0.668 / Rpim(I) all: 0.429 / Rsym value: 0.691 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6XC4,4IMK,2Q20 Resolution: 2.89→42.77 Å / SU ML: 0.4316 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 30.5748 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 47.36 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.89→42.77 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 32.6080084968 Å / Origin y: -24.9837704453 Å / Origin z: 36.0594463637 Å
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Refinement TLS group | Selection details: all |