Plasmodium falciparum adhesive protein that mediates sequestration of parasite‐infected red blood in human placenta and cause pregnancy specific malaria

Malaria caused by Plasmodium falciparum results in millions of deaths every year. In endemic areas, although immunity to malaria develops during childhood years, women become susceptible to malaria during pregnancy. This is due to the sequestration of P. falciparum infected erythrocytes (IEs) in the placenta by binding to host chondroitin 4‐sulfate (C4S). A parasite protein called var 2CSA, a member of antigenically diverse family of 60 parasite proteins expressed on the erythrocyte membrane is involved in IE adherence to C4S. Var 2‐CSA consists of several D uffy b inding l ike (DBL) domains and how exactly they bind C4S remain unclear. We expressed various DBL domains on yeast cell surface and analyzed cell adherence to C4S. None of the DBL domains could support binding of yeast to C4S, suggesting that individual DBL domains cannot support IRBC binding. It is possible that a conformational structure involving two or more domains is involved in IRBC binding. Alternatively, var 2CSA alone may not be sufficient for IE binding, instead a multiprotein complex is involved. To test this hypothesis, we performed affinity binding of parasite ligand from the lysates of 35 S‐labeled IEs using C4S‐conjugated beads. In addition to var2 CSA, several other proteins could specifically bind to C4S‐beads. Together these data suggest that a complex of var 2CSA and other proteins is involved in IE binding. Funded by AI45086 from NIAID, NIH.