View source for 2xu0


==Crystal structure of the NTS-DBL1(alpha-1) domain of the Plasmodium falciparum membrane protein 1 (PfEMP1) from the varO strain.==
<StructureSection load='2xu0' size='340' side='right'caption='[[2xu0]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xu0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_Palo_Alto/Uganda Plasmodium falciparum Palo Alto/Uganda]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XU0 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]] 2.06&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PRO:PROLINE'>PRO</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=2xu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xu0 OCA], [https://pdbe.org/2xu0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xu0 RCSB], [https://www.ebi.ac.uk/pdbsum/2xu0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xu0 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 human malaria parasite Plasmodium falciparum can cause infected red blood cells (iRBC) to form rosettes with uninfected RBC, a phenotype associated with severe malaria. Rosetting is mediated by a subset of the Plasmodium falciparum membrane protein 1 (PfEMP1) variant adhesins expressed on the infected host-cell surface. Heparin and other sulfated oligosaccharides, however, can disrupt rosettes, suggesting that therapeutic approaches to this form of severe malaria are feasible. We present a structural and functional study of the N-terminal domain of PfEMP1 from the VarO variant comprising the N-terminal segment (NTS) and the first DBL domain (DBL1alpha(1)), which is directly implicated in rosetting. We demonstrate that NTS-DBL1alpha(1)-VarO binds to RBC and that heparin inhibits this interaction in a dose-dependent manner, thus mimicking heparin-mediated rosette disruption. We have determined the crystal structure of NTS-DBL1alpha(1), showing that NTS, previously thought to be a structurally independent component of PfEMP1, forms an integral part of the DBL1alpha domain. Using mutagenesis and docking studies, we have located the heparin-binding site, which includes NTS. NTS, unique to the DBL alpha-class domain, is thus an intrinsic structural and functional component of the N-terminal VarO domain. The specific interaction observed with heparin opens the way for developing antirosetting therapeutic strategies.

Structure of a Plasmodium falciparum PfEMP1 rosetting domain reveals a role for the N-terminal segment in heparin-mediated rosette inhibition.,Juillerat A, Lewit-Bentley A, Guillotte M, Gangnard S, Hessel A, Baron B, Vigan-Womas I, England P, Mercereau-Puijalon O, Bentley GA Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5243-8. Epub 2011 Mar 14. PMID:21402930<ref>PMID:21402930</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2xu0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum Palo Alto/Uganda]]
[[Category: Bentley GA]]
[[Category: England P]]
[[Category: Gangnard S]]
[[Category: Guillotte M]]
[[Category: Hessler A]]
[[Category: Juillerat A]]
[[Category: Lewit-Bentley A]]
[[Category: Mercereau-Puijalon O]]
[[Category: Vigan-Womas I]]