7JXD

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: 2.50 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.206 

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
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
S2A4 antigen-binding (Fab) fragmentAC228Homo sapiensMutation(s): 0 
Protein Feature View
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 2
MoleculeChainsSequence LengthOrganismDetailsImage
S2A4 antigen-binding (Fab) fragmentBD217Homo sapiensMutation(s): 0 
Protein Feature View
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.206 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 59.091α = 90
b = 63.285β = 103.97
c = 113.895γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
DENZOdata reduction
HKL-2000data scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM120553

Revision History 

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