2YK0

Structure of the N-terminal NTS-DBL1-alpha and CIDR-gamma double domain of the PfEMP1 protein from Plasmodium falciparum varO strain.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural Basis for the Abo Blood-Group Dependence of Plasmodium Falciparum Rosetting.

Vigan-Womas, I.Guillotte, M.Juillerat, A.Hessel, A.Raynal, B.England, P.Cohen, J.H.Bertrand, O.Peyrard, T.Bentley, G.A.Lewit-Bentley, A.Mercereau-Puijalon, O.

(2012) PLoS Pathog 8: 2781

  • DOI: https://doi.org/10.1371/journal.ppat.1002781
  • Primary Citation of Related Structures:  
    2YK0

  • PubMed Abstract: 

    The ABO blood group influences susceptibility to severe Plasmodium falciparum malaria. Recent evidence indicates that the protective effect of group O operates by virtue of reduced rosetting of infected red blood cells (iRBCs) with uninfected RBCs. Rosetting is mediated by a subgroup of PfEMP1 adhesins, with RBC binding being assigned to the N-terminal DBL1α₁ domain. Here, we identify the ABO blood group as the main receptor for VarO rosetting, with a marked preference for group A over group B, which in turn is preferred to group O RBCs. We show that recombinant NTS-DBL1α₁ and NTS-DBL1α₁-CIDR1γ reproduce the VarO-iRBC blood group preference and document direct binding to blood group trisaccharides by surface plasmon resonance. More detailed RBC subgroup analysis showed preferred binding to group A₁, weaker binding to groups A₂ and B, and least binding to groups A(x) and O. The 2.8 Å resolution crystal structure of the PfEMP1-VarO Head region, NTS-DBL1α₁-CIDR1γ, reveals extensive contacts between the DBL1α₁ and CIDR1γ and shows that the NTS-DBL1α₁ hinge region is essential for RBC binding. Computer docking of the blood group trisaccharides and subsequent site-directed mutagenesis localized the RBC-binding site to the face opposite to the heparin-binding site of NTS-DBLα₁. RBC binding involves residues that are conserved between rosette-forming PfEMP1 adhesins, opening novel opportunities for intervention against severe malaria. By deciphering the structural basis of blood group preferences in rosetting, we provide a link between ABO blood grouppolymorphisms and rosette-forming adhesins, consistent with the selective role of falciparum malaria on human genetic makeup.


  • Organizational Affiliation

    Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, Paris, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ERYTHROCYTE MEMBRANE PROTEIN 1790Plasmodium falciparumMutation(s): 8 
UniProt
Find proteins for B7T1P0 (Plasmodium falciparum)
Explore B7T1P0 
Go to UniProtKB:  B7T1P0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupB7T1P0
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 157.907α = 90
b = 144.362β = 102.89
c = 75.836γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-30
    Type: Initial release
  • Version 1.1: 2012-08-01
    Changes: Database references
  • Version 1.2: 2019-03-06
    Changes: Data collection, Experimental preparation, Other
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description