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- PDB-7jmx: Crystal structure of a SARS-CoV-2 cross-neutralizing antibody COV... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7jmx | |||||||||
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Title | Crystal structure of a SARS-CoV-2 cross-neutralizing antibody COVA1-16 Fab | |||||||||
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![]() | IMMUNE SYSTEM / SARS-CoV-2 / Antibody / Spike / Coronavirus / COVID-19 | |||||||||
Function / homology | ACETATE ION![]() | |||||||||
Biological species | ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Liu, H. / Yuan, M. / Zhu, X. / Wu, N.C. / Wilson, I.A. | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 211.1 KB | Display | ![]() |
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PDB format | ![]() | 140 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 457.9 KB | Display | ![]() |
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Full document | ![]() | 460.7 KB | Display | |
Data in XML | ![]() | 17 KB | Display | |
Data in CIF | ![]() | 23 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7jmwC ![]() 2q20S ![]() 4imkS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Unit cell |
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Components on special symmetry positions |
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Components
#1: Antibody | Mass: 25928.943 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||||
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#2: Antibody | Mass: 23415.799 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||||
#3: Chemical | #4: Chemical | ChemComp-ACT / | #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.22 Å3/Da / Density % sol: 61.84 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop / pH: 4.6 Details: 20% glycerol, 20% PEG-4000, 0.16 M NH4-sulfate, 0.08 M acetate pH 4.6 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 24, 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: 2.53→50 Å / Num. obs: 22357 / % possible obs: 100 % / Redundancy: 37 % / Biso Wilson estimate: 40.4 Å2 / CC1/2: 0.996 / Rpim(I) all: 0.038 / Rsym value: 0.236 / Net I/σ(I): 21.5 |
Reflection shell | Resolution: 2.53→2.58 Å / Num. unique obs: 1084 / CC1/2: 0.521 / Rpim(I) all: 0.543 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4IMK,2Q20 Resolution: 2.53→30.65 Å / SU ML: 0.337 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 24.6673 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: 43.02 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.53→30.65 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: 9.17418363294 Å / Origin y: 0.657976284927 Å / Origin z: -30.7250073355 Å
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Refinement TLS group | Selection details: all |