Structure of the DBL3X-DBL4ε region of the VAR2CSA placental malaria vaccine candidate: insight into DBL domain interactions.
In: Scientific Reports, 2015-10-09, S. 1-11
Online
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Zugriff:
The human malaria parasite, Plasmodium falciparum, is able to evade spleen-mediated clearing from blood stream by sequestering in peripheral organs. This is due to the adhesive properties conferred by the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family exported by the parasite to the surface of infected erythrocytes. Expression of the VAR2CSA variant of PfEMP1 leads to pregnancy-associated malaria, which occurs when infected erythrocytes massively sequester in the placenta by binding to low-sulfated Chondroitin Sulfate A (CSA) present in the intervillous spaces. VAR2CSA is a 350 kDa protein that carries six Duffy-Binding Like (DBL) domains, one Cysteine-rich Inter-Domain Regions (CIDR) and several inter-domain regions. In the present paper, we report for the first time the crystal structure at 2.9 Å of a VAR2CSA double domain, DBL3X-DBL4ε, from the FCR3 strain. DBL3X and DBL4ε share a large contact interface formed by residues that are invariant or highly conserved in VAR2CSA variants, which suggests that these two central DBL domains (DBL3X-DBL4ε) contribute significantly to the structuring of the functional VAR2CSA extracellular region. We have also examined the antigenicity of peptides corresponding to exposed loop regions of the DBL4ε structure. [ABSTRACT FROM AUTHOR]
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Structure of the DBL3X-DBL4ε region of the VAR2CSA placental malaria vaccine candidate: insight into DBL domain interactions.
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Autor/in / Beteiligte Person: | Gangnard, Stéphane ; Lewit-Bentley, Anita ; Dechavanne, Sébastien ; Srivastava, Anand ; Amirat, Faroudja ; Bentley, Graham A. ; Gamain, Benoît |
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Zeitschrift: | Scientific Reports, 2015-10-09, S. 1-11 |
Veröffentlichung: | 2015 |
Medientyp: | academicJournal |
ISSN: | 2045-2322 (print) |
DOI: | 10.1038/srep14868 |
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