View source for 6s8t


==Structure of the ICAM-1-binding PfEMP1 IT4var13 DBLbeta domain==
<StructureSection load='6s8t' size='340' side='right'caption='[[6s8t]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6s8t]] 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=6S8T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S8T 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]] 2.17&#8491;</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=6s8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s8t OCA], [https://pdbe.org/6s8t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s8t RCSB], [https://www.ebi.ac.uk/pdbsum/6s8t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s8t ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/E0A3B3_PLAFA E0A3B3_PLAFA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A major determinant of pathogenicity in malaria caused by Plasmodium falciparum is the adhesion of parasite-infected erythrocytes to the vasculature or tissues of infected individuals. This occludes blood flow, leads to inflammation, and increases parasitemia by reducing spleen-mediated clearance of the parasite. This adhesion is mediated by PfEMP1, a multivariant family of around 60 proteins per parasite genome which interact with specific host receptors. One of the most common of these receptors is intracellular adhesion molecule-1 (ICAM-1), which is bound by 2 distinct groups of PfEMP1, A-type and B or C (BC)-type. Here, we present the structure of a domain from a B-type PfEMP1 bound to ICAM-1, revealing a complex binding site. Comparison with the existing structure of an A-type PfEMP1 bound to ICAM-1 shows that the 2 complexes share a globally similar architecture. However, while the A-type PfEMP1 bind ICAM-1 through a highly conserved binding surface, the BC-type PfEMP1 use a binding site that is more diverse in sequence, similar to how PfEMP1 interact with other human receptors. We also show that A- and BC-type PfEMP1 present ICAM-1 at different angles, perhaps influencing the ability of neighboring PfEMP1 domains to bind additional receptors. This illustrates the deep diversity of the PfEMP1 and demonstrates how variations in a single domain architecture can modulate binding to a specific ligand to control function and facilitate immune evasion.

Structural insights into diverse modes of ICAM-1 binding by Plasmodium falciparum-infected erythrocytes.,Lennartz F, Smith C, Craig AG, Higgins MK Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):20124-20134. doi:, 10.1073/pnas.1911900116. Epub 2019 Sep 16. PMID:31527263<ref>PMID:31527263</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6s8t" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Higgins MK]]
[[Category: Lennartz F]]