View source for 2yk0


==Structure of the N-terminal NTS-DBL1-alpha and CIDR-gamma double domain of the PfEMP1 protein from Plasmodium falciparum varO strain.==
<StructureSection load='2yk0' size='340' side='right'caption='[[2yk0]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2yk0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YK0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2yk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yk0 OCA], [https://pdbe.org/2yk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yk0 RCSB], [https://www.ebi.ac.uk/pdbsum/2yk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yk0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B7T1P0_PLAFA B7T1P0_PLAFA] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:22807674</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2yk0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Bentley GA]]
[[Category: Guillotte M]]
[[Category: Hessel A]]
[[Category: Juillerat A]]
[[Category: Lewit-Bentley A]]
[[Category: Mercereau-Puijalon O]]
[[Category: Raynal B]]
[[Category: Vigan-Womas I]]