Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family

The plasmodium falciparum erythrocyte membrane protein 1 (pfemp1) family plays a central role in antigenic variation and cytoadhesion of p. falciparum infected erythrocytes. pfemp1 proteins/var genes are classified into three main subfamilies (upsa,upsb,and upsc) that are hypothesized to have different roles in binding and disease. to investigate whether these subfamilies have diverged in binding specificity and test if binding could be predicted by adhesion domain classification,we generated a panel of 19 parasite lines that primarily expressed a single dominant var transcript and assayed binding against 12 known host receptors. by limited dilution cloning,only upsb and upsc var genes were isolated,indicating that upsa var gene expression is rare under in vitro culture conditions. consequently,three upsa variants were obtained by rosette purification and selection with specific monoclonal antibodies to create a more representative panel. binding assays showed that cd36 was the most common adhesion partner of the parasite panel,followed by icam-1 and tsp-1,and that cd36 and icam-1 binding variants were highly predicted by adhesion domain sequence classification. binding to other host receptors,including csa,vcam-1,habp1,cd31/pecam,e-selectin,endoglin,cho receptor x