7JX3

Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.288 
  • R-Value Work: 0.258 
  • R-Value Observed: 0.259 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology.

Piccoli, L.Park, Y.J.Tortorici, M.A.Czudnochowski, N.Walls, A.C.Beltramello, M.Silacci-Fregni, C.Pinto, D.Rosen, L.E.Bowen, J.E.Acton, O.J.Jaconi, S.Guarino, B.Minola, A.Zatta, F.Sprugasci, N.Bassi, J.Peter, A.De Marco, A.Nix, J.C.Mele, F.Jovic, S.Rodriguez, B.F.Gupta, S.V.Jin, F.Piumatti, G.Lo Presti, G.Pellanda, A.F.Biggiogero, M.Tarkowski, M.Pizzuto, M.S.Cameroni, E.Havenar-Daughton, C.Smithey, M.Hong, D.Lepori, V.Albanese, E.Ceschi, A.Bernasconi, E.Elzi, L.Ferrari, P.Garzoni, C.Riva, A.Snell, G.Sallusto, F.Fink, K.Virgin, H.W.Lanzavecchia, A.Corti, D.Veesler, D.

(2020) Cell 183: 1024-1042.e21

  • DOI: 10.1016/j.cell.2020.09.037
  • Primary Citation of Related Structures:  
    7JVA, 7JV6, 7JV4, 7JV2, 7JW0, 7JVC, 7JXC, 7JXD, 7JX3, 7JXE

  • PubMed Abstract: 
  • Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we ...

    Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.


    Organizational Affiliation

    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu.



Macromolecules
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Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Light chain of Fab domain of monoclonal antibody S309B214Homo sapiensMutation(s): 0 
Protein Feature View
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  • Reference Sequence
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Entity ID: 2
MoleculeChainsSequence LengthOrganismDetailsImage
Heavy chain of Fab domain of monoclonal antibody S309A230Homo sapiensMutation(s): 0 
Protein Feature View
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Entity ID: 3
MoleculeChainsSequence LengthOrganismDetailsImage
Light chain of Fab domain of monoclonal antibody S2H14D216Homo sapiensMutation(s): 0 
Protein Feature View
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Entity ID: 4
MoleculeChainsSequence LengthOrganismDetailsImage
Heavy chain of Fab domain of monoclonal antibody S2H14C229Homo sapiensMutation(s): 0 
Protein Feature View
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Entity ID: 5
MoleculeChainsSequence LengthOrganismDetailsImage
Light chain of Fab domain of monoclonal antibody S304L215Homo sapiensMutation(s): 0 
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Entity ID: 6
MoleculeChainsSequence LengthOrganismDetailsImage
Heavy chain of Fab domain of monoclonal antibody S304H223Homo sapiensMutation(s): 0 
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Entity ID: 7
MoleculeChainsSequence LengthOrganismDetailsImage
Spike glycoproteinR204Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
Gene Names: S2
Find proteins for P0DTC2 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTC2 
Go to UniProtKB:  P0DTC2
Protein Feature View
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download CCD File 
R
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.288 
  • R-Value Work: 0.258 
  • R-Value Observed: 0.259 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.54α = 90
b = 127.78β = 96.66
c = 192.28γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM120553
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesSeattle Structural Genomics Center for Infectious Diseases (SSGCID)

Revision History 

  • Version 1.0: 2020-10-14
    Type: Initial release
  • Version 1.1: 2020-11-25
    Changes: Database references