Structural insights into chondroitin sulfate binding in pregnancy-associated malaria

Malaria during pregnancy is caused when parasite-infected erythrocytes accumulate within the placenta through interactions between the VAR2CSA protein on the infected erythrocyte surface and placental CSPGs (chondroitin sulfate proteoglycans). This interaction is the major target for therapeutics to treat or prevent pregnancy-associated malaria. Here we review the structural characterization of CSPG-binding DBL (Duffy-binding like) domains from VAR2CSA and summarize the growing evidence that the exquisite ligand specificity of VAR2CSA results from the adoption of higher-order architecture in which these domains fold together to form a ligand-binding pocket.