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- PDB-7jmx: Crystal structure of a SARS-CoV-2 cross-neutralizing antibody COV... -

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Basic information

Entry
Database: PDB / ID: 7jmx
TitleCrystal structure of a SARS-CoV-2 cross-neutralizing antibody COVA1-16 Fab
Components
  • COVA1-16 heavy chain
  • COVA1-16 light chain
KeywordsIMMUNE SYSTEM / SARS-CoV-2 / Antibody / Spike / Coronavirus / COVID-19
Function / homologyACETATE ION
Function and homology information
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.53 Å
AuthorsLiu, H. / Yuan, M. / Zhu, X. / Wu, N.C. / Wilson, I.A.
Funding support United States, 2items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationOPP1170236 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI139445 United States
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
DepositionAug 3, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 14, 2020Provider: repository / Type: Initial release
Revision 1.1Dec 16, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Dec 30, 2020Group: Database references / Category: citation / citation_author
Revision 1.3Feb 9, 2022Group: Database references / Category: citation / citation_author / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / pdbx_initial_refinement_model
Item: _citation.journal_id_ISSN

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: COVA1-16 heavy chain
L: COVA1-16 light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,6926
Polymers49,3452
Non-polymers3474
Water75742
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3880 Å2
ΔGint-52 kcal/mol
Surface area18550 Å2
MethodPISA
Unit cell
Length a, b, c (Å)156.287, 156.287, 156.287
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number213
Space group name H-MP4132
Space group name HallP4bd2ab3
Symmetry operation#1: x,y,z
#2: x+1/4,-z+1/4,y+3/4
#3: x+3/4,z+1/4,-y+1/4
#4: z+3/4,y+1/4,-x+1/4
#5: -z+1/4,y+3/4,x+1/4
#6: -y+1/4,x+3/4,z+1/4
#7: y+1/4,-x+1/4,z+3/4
#8: z,x,y
#9: y,z,x
#10: -y+1/2,-z,x+1/2
#11: z+1/2,-x+1/2,-y
#12: -y,z+1/2,-x+1/2
#13: -z+1/2,-x,y+1/2
#14: -z,x+1/2,-y+1/2
#15: y+1/2,-z+1/2,-x
#16: x+1/2,-y+1/2,-z
#17: -x,y+1/2,-z+1/2
#18: -x+1/2,-y,z+1/2
#19: y+3/4,x+1/4,-z+1/4
#20: -y+3/4,-x+3/4,-z+3/4
#21: z+1/4,-y+1/4,x+3/4
#22: -z+3/4,-y+3/4,-x+3/4
#23: -x+1/4,z+3/4,y+1/4
#24: -x+3/4,-z+3/4,-y+3/4
Components on special symmetry positions
IDModelComponents
11H-303-

SO4

21H-303-

SO4

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Components

#1: Antibody COVA1-16 heavy chain


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)
#2: Antibody COVA1-16 light chain


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)
#3: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-ACT / ACETATE ION / Acetate


Mass: 59.044 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H3O2
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 42 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 3.22 Å3/Da / Density % sol: 61.84 %
Crystal growTemperature: 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

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-1 / Wavelength: 0.9795 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 24, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 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 shellResolution: 2.53→2.58 Å / Num. unique obs: 1084 / CC1/2: 0.521 / Rpim(I) all: 0.543

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Processing

Software
NameVersionClassification
MOLREP5.8.0258refinement
PHENIX1.16_3549refinement
HKL-2000data reduction
HKL-2000data scaling
PHASER2.8.3phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4IMK,2Q20

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
RfactorNum. reflection% reflection
Rfree0.2439 1069 4.89 %
Rwork0.2115 20805 -
obs0.2131 21874 98.09 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 43.02 Å2
Refinement stepCycle: LAST / Resolution: 2.53→30.65 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3223 0 19 42 3284
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00723312
X-RAY DIFFRACTIONf_angle_d1.00944518
X-RAY DIFFRACTIONf_chiral_restr0.0573514
X-RAY DIFFRACTIONf_plane_restr0.0059580
X-RAY DIFFRACTIONf_dihedral_angle_d3.76291957
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.53-2.650.34271390.30592271X-RAY DIFFRACTION88.12
2.65-2.790.30741260.2772590X-RAY DIFFRACTION99.82
2.79-2.960.29531330.26152594X-RAY DIFFRACTION100
2.96-3.190.29661370.23942615X-RAY DIFFRACTION99.96
3.19-3.510.23411410.22422602X-RAY DIFFRACTION100
3.51-4.020.2271360.19352658X-RAY DIFFRACTION99.86
4.02-5.060.19471340.16692681X-RAY DIFFRACTION99.96
5.06-30.650.22551230.19422794X-RAY DIFFRACTION96.97
Refinement TLS params.Method: refined / Origin x: 9.17418363294 Å / Origin y: 0.657976284927 Å / Origin z: -30.7250073355 Å
111213212223313233
T0.137029029398 Å2-0.0411351010443 Å2-0.0276820170249 Å2-0.183772546995 Å20.00817884545816 Å2--0.138788507579 Å2
L0.278824783037 °20.25382783285 °2-0.593484280611 °2-0.980678618787 °2-0.592264786061 °2--0.913055090486 °2
S-0.0872312019237 Å °0.0630077130588 Å °0.00867107958984 Å °-0.0529839880791 Å °0.157828309078 Å °-0.091114367579 Å °0.132769031534 Å °-0.0798552686004 Å °0.0218113065894 Å °
Refinement TLS groupSelection details: all

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