Identification of glycosaminoglycan binding domains in Plasmodium falciparum erythrocyte membrane protein 1 of a chondroitin sulfate A-adherent parasite

Accumulation of Plasmodium falciparum-infected erythrocytes in the placenta is a key feature of maternal malaria. This process is mediated in part by the parasite ligand P, falciparum erythrocyte membrane protein 1 (PfEMP1) a t the surface of the infected erythrocyte interacting with the host recepto r chondroitin sulfate A (CSA) on the placental lining. We have localized CS A binding activity to two adjacent domains in PfEMP1 of an adherent parasit e line and shown the presence of at least three active glycosaminoglycan bi nding sites. A putative CSA binding sequence was identified in one domain, but nonlinear binding motifs are also likely to be present, since binding a ctivity in the region was shown to be dependent on conformation. Characteri zation of this binding region provides an opportunity to investigate furthe r its potential as a target for antiadhesion therapy.