4P1T

Crystal structure of the DBL3X-DBL4epsilon double domain from the extracellular part of VAR2CSA PfEMP1 from Plasmodium falciparum

Summary for 4P1T

• Entry DOI: 10.2210/pdb4p1t/pdb
• Related: 2WAU 3CML
• Descriptor: Erythrocyte membrane protein 1 (2 entities in total)
• Functional Keywords: pfemp1, csa, dbl fold, membrane protein
• Biological source: Plasmodium falciparum
• Total number of polymer chains: 1
• Total formula weight: 86439.62

Authors

Gangnard, S.,Dechavanne, S.,Srivastava, A.,Amirat, F.,Gamain, B.,Lewit-Bentley, A.,Bentley, G.A. (deposition date: 2014-02-27, release date: 2015-03-04, Last modification date: 2024-10-23)

Primary citation

Gangnard, S.,Lewit-Bentley, A.,Dechavanne, S.,Srivastava, A.,Amirat, F.,Bentley, G.A.,Gamain, B.
Structure of the DBL3X-DBL4 epsilon region of the VAR2CSA placental malaria vaccine candidate: insight into DBL domain interactions.
Sci Rep, 5:14868-14868, 2015

PubMed 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.

PubMed: 26450557
DOI: 10.1038/srep14868

Experimental method

X-RAY DIFFRACTION (2.9 Å)