6E63

Crystal structure of malaria transmission-blocking antigen Pfs48/45 6C in complex with antibody TB31F


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 

wwPDB Validation   3D Report Full Report


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Literature

Structural delineation of potent transmission-blocking epitope I on malaria antigen Pfs48/45.

Kundu, P.Semesi, A.Jore, M.M.Morin, M.J.Price, V.L.Liang, A.Li, J.Miura, K.Sauerwein, R.W.King, C.R.Julien, J.P.

(2018) Nat Commun 9: 4458-4458

  • DOI: https://doi.org/10.1038/s41467-018-06742-9
  • Primary Citation of Related Structures:  
    6E62, 6E63, 6E64, 6E65

  • PubMed Abstract: 

    Interventions that can block the transmission of malaria-causing Plasmodium falciparum (Pf) between the human host and Anopheles vector have the potential to reduce the incidence of malaria. Pfs48/45 is a gametocyte surface protein critical for parasite development and transmission, and its targeting by monoclonal antibody (mAb) 85RF45.1 leads to the potent reduction of parasite transmission. Here, we reveal how the Pfs48/45 6C domain adopts a (SAG1)-related-sequence (SRS) fold. We structurally delineate potent epitope I and show how mAb 85RF45.1 recognizes an electronegative surface with nanomolar affinity. Analysis of Pfs48/45 sequences reveals that polymorphisms are rare for residues involved at the binding interface. Humanization of rat-derived mAb 85RF45.1 conserved the mode of recognition and activity of the parental antibody, while also improving its thermostability. Our work has implications for the development of transmission-blocking interventions, both through improving vaccine designs and the testing of passive delivery of mAbs in humans.


  • Organizational Affiliation

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


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Pf48/45A [auth P],
D [auth A]
138Plasmodium falciparumMutation(s): 0 
UniProt
Find proteins for Q8I6T1 (Plasmodium falciparum (isolate 3D7))
Explore Q8I6T1 
Go to UniProtKB:  Q8I6T1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8I6T1
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
TB31F Fab heavy chainB [auth H],
E [auth B]
222Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
TB31F Fab light chainC [auth L],
F [auth C]
215Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 
  • Space Group: P 2 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.994α = 90
b = 120.907β = 90
c = 177.562γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Bill & Melinda Gates FoundationUnited StatesOPP1108403

Revision History  (Full details and data files)

  • Version 1.0: 2018-11-28
    Type: Initial release