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Var2CSA Minimal CSA Binding Region Is Located within the N-Terminal Region 1,2,3,4,5 ´ 1,2,3,4,5 ´ 1,2,3,4,5 1,2 Anand Srivastava , Stephane Gangnard , Sebastien Dechavanne , Farroudja Amirat , 1,2 1,2 ˆ 3,4,5 Anita Lewit Bentley , Graham A. Bentley , Benoıt Gamain * ´ 1 Institut Pasteur, Unite d’Immunologie Structurale, F-75015 Paris, France, 2 CNRS, URA2185, F-75015 Paris, France, 3 INSERM, U665, F-75739 Paris, France, 4 Institut ´ ´ ´ National de la Transfusion Sanguine, F-75739 Paris, France, 5 Univ Paris Diderot, Sorbonne Paris Cite, Proteines de la membrane erythrocytaire, UMR-S665, F-75739 Paris, France Abstract Var2CSA, a key molecule linked with pregnancy-associated malaria (PAM), causes sequestration of Plasmodium falciparum infected erythrocytes (PEs) in the placenta by adhesion to chondroitin sulfate A (CSA). Var2CSA possesses a 300 kDa extracellular region composed of six Duffy-binding like (DBL) domains and a cysteine-rich interdomain region (CIDRpam) module. Although initial studies implicated several individual var2CSA DBL domains as important for adhesion of PEs to CSA, new studies revealed that these individual domains lack both the affinity and specificity displayed by the full-length extracellular region. Indeed, recent evidence suggests the presence of a single CSA-binding site formed by a higher-order domain organization rather than severa