2yk0

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

spinqualitylabelsall models 2yk0, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2yk0 is a 1 chain structure with sequence from Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B7T1P0_PLAFA Publication Abstract from PubMed 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 DBL1alpha(1) 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-DBL1alpha(1) and NTS-DBL1alpha(1)-CIDR1gamma 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 A(1), weaker binding to groups A(2) and B, and least binding to groups A(x) and O. The 2.8 A resolution crystal structure of the PfEMP1-VarO Head region, NTS-DBL1alpha(1)-CIDR1gamma, reveals extensive contacts between the DBL1alpha(1) and CIDR1gamma and shows that the NTS-DBL1alpha(1) 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-DBLalpha(1). 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. 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 JH, Bertrand O, Peyrard T, Bentley GA, Lewit-Bentley A, Mercereau-Puijalon O PLoS Pathog. 2012 Jul;8(7):e1002781. Epub 2012 Jul 12. PMID:22807674 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA