6B08

Crystal structure of Pfs25 in complex with the transmission blocking antibody 1276


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.

Scally, S.W.McLeod, B.Bosch, A.Miura, K.Liang, Q.Carroll, S.Reponen, S.Nguyen, N.Giladi, E.Ramisch, S.Yusibov, V.Bradley, A.Lemiale, F.Schief, W.R.Emerling, D.Kellam, P.King, C.R.Julien, J.P.

(2017) Nat Commun 8: 1568-1568

  • DOI: https://doi.org/10.1038/s41467-017-01924-3
  • Primary Citation of Related Structures:  
    6AZZ, 6B08, 6B0A, 6B0E, 6B0G, 6B0H

  • PubMed Abstract: 

    The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.


  • Organizational Affiliation

    Program in Molecular Medicine, The Hospital for Sick Children Research Institute, 686 Bay St, Toronto, ON, Canada, M5G 0A4.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
1276 antibody, heavy chainA [auth C]223Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
1276 antibody, light chain213Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Pfs25C [auth A]183Plasmodium falciparumMutation(s): 0 
UniProt
Find proteins for P13829 (Plasmodium falciparum (isolate NF54))
Explore P13829 
Go to UniProtKB:  P13829
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP13829
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 139.351α = 90
b = 70.264β = 90.45
c = 83.742γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XPREPdata scaling
PHENIXphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-11-15
    Type: Initial release
  • Version 1.1: 2017-11-29
    Changes: Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description