Abstract |
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.
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Authors | Stéphane Gangnard, Anita Lewit-Bentley, Sébastien Dechavanne, Anand Srivastava, Faroudja Amirat, Graham A Bentley, Benoît Gamain |
Journal | Scientific reports
(Sci Rep)
Vol. 5
Pg. 14868
(Oct 09 2015)
ISSN: 2045-2322 [Electronic] England |
PMID | 26450557
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Protozoan
- Antigens, Protozoan
- Immune Sera
- Malaria Vaccines
- VAR2CSA protein, Plasmodium falciparum
- Chondroitin Sulfates
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Topics |
- Amino Acid Sequence
- Animals
- Antibodies, Protozoan
(blood, immunology)
- Antigens, Protozoan
(chemistry, genetics, immunology)
- Binding Sites
(genetics, immunology)
- Chondroitin Sulfates
(immunology, metabolism)
- Crystallography, X-Ray
- Erythrocytes
(immunology, parasitology)
- Female
- Host-Parasite Interactions
(immunology)
- Humans
- Immune Sera
(immunology)
- Malaria Vaccines
(administration & dosage, immunology)
- Malaria, Falciparum
(immunology, parasitology, prevention & control)
- Models, Molecular
- Molecular Sequence Data
- Mutation
- Placenta
(immunology, metabolism, parasitology)
- Plasmodium falciparum
(immunology, metabolism, physiology)
- Pregnancy
- Protein Binding
(immunology)
- Protein Structure, Tertiary
- Rabbits
- Sequence Homology, Amino Acid
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