6WFZ

Crystal structure of Fab399 in complex with NPNA3 peptide from circumsporozoite protein


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum.

Pholcharee, T.Oyen, D.Flores-Garcia, Y.Gonzalez-Paez, G.Han, Z.Williams, K.L.Volkmuth, W.Emerling, D.Locke, E.Richter King, C.Zavala, F.Wilson, I.A.

(2021) Nat Commun 12: 1063-1063

  • DOI: https://doi.org/10.1038/s41467-021-21221-4
  • Primary Citation of Related Structures:  
    6W00, 6W05, 6WFW, 6WFX, 6WFY, 6WFZ, 6WG0, 6WG1, 6WG2

  • PubMed Abstract: 

    The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes. The structures reinforce the importance of homotypic Fab-Fab interactions in protective antibodies and the overwhelmingly dominant preference for a germline-encoded aromatic residue for recognition of the NANP motif. In this study, antibody apparent affinity correlates best with protection in an in vivo mouse model, with the more potent antibodies also recognizing epitopes with repeating secondary structural motifs of type I β- and Asn pseudo 3 10 turns; such insights can be incorporated into design of more effective immunogens and antibodies for passive immunization.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fab399 heavy chainA,
D [auth H]
224Homo sapiensMutation(s): 0 
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Fab399 light chainB,
E [auth L]
219Homo sapiensMutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
NPNA3 peptideC,
F [auth P]
14Plasmodium falciparumMutation(s): 0 
UniProt
Find proteins for P02893 (Plasmodium falciparum)
Explore P02893 
Go to UniProtKB:  P02893
Entity Groups  
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UniProt GroupP02893
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.395α = 90
b = 87.604β = 101.06
c = 89.645γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Bill & Melinda Gates FoundationUnited StatesOPP1170236

Revision History  (Full details and data files)

  • Version 1.0: 2020-07-29
    Type: Initial release
  • Version 1.1: 2021-03-03
    Changes: Database references