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Crystal structure of VAR2CSA DBL3x domain

VAR2CSA is a 350 kDa transmembrane protein and has been identified as the only gene overexpressed by Plasmodium falciparum infected erythrocytes selected to adhere to CSA. The resulting protein is the major receptor responsible for the adhesion of EI (infected erythrocytes) to the placenta. We were able to identify it by the antibodies present in the body of pregnant women infected with P. falciparum. Its extracellular part is composed of 6 known (epsilon) or unknown (x) domains, interspersed with Cysteine-rich Inter-Domain Regions (CIDR) and TM and ATS regions (Acidic Terminal Segment) including DBL3x. In fact, Duffy Binding-Like 3 x domain (DBL3x) is one of the six DBL domains of the variant surface antigen 2 CSA, belonging to the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family and involved in Pregnancy-Associated Malaria.

3D model of DBL3x domain

Drag the structure with the mouse to rotate

References

Ref 1. Singh SK, Hora R, Belrhali H, Chitnis CE, Sharma A. Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain. Nature. 2006;439:741–744. https://www.ncbi.nlm.nih.gov/pubmed/17224156

Ref 2. Kavita Singh, Apostolos G Gittis, Phuc Nguyen, D Channe Gowda, Louis H Miller and David N Garboczi1, Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658892/, accessed on 27.12.17 at 8 p.m.

Ref 3. Stéphane Gangnard, Anita Lewit-Bentley, Sébastien Dechavanne, Anand Srivastava, Faroudja Amirat, Graham A. Bentley & Benoît Gamain, Structure of the DBL3X-DBL4ε region of the VAR2CSA placental malaria vaccine candidate: insight into DBL domain interactions, http://www.nature.com/articles/srep14868, consulted on 03/01/2017.

Ref 4.Graham A Bentley & Benoît Gamain, A schematic representation of the VAR2CSA PfEMP1 variant anchored to the membrane of the infected erythrocyte, http://www.nature.com/nsmb/journal/v15/n9/fig_tab/nsmb0908-895_F1.html, consulted on 10/01/17.

Ref5. Pongsak Khunrae, Judith M.D. Philip, Duncan R. Bull, Matthew K. Higgins, Structural Comparison of Two CSPG-Binding DBL Domains from the VAR2CSA Protein Important in Malaria during Pregnancy. Department of Biochemistry, University of Cambridge, 80, Tennis Court Road, Cambridge CB2 1GA, UK http://www.sciencedirect.com/science/article/pii/S0022283609010237, consulted on 05/01/2017

Ref6. Madeleine Dahlbäck, Lars M. Jørgensen, Morten A. Nielsen, Thomas M. Clausen, Sisse B. Ditlev, Mafalda Resende, Vera V. Pinto, David E. Arnot, Thor G. Theander, and Ali Salanti, The Chondroitin Sulfate A-binding Site of the VAR2CSA Protein Involves Multiple N-terminal Domains. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091200/ consulted on 15/01/2017

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Margaux Boutet

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