Protein-protein interaction studies reveal the Merozoite surface protein-1 region involved in complex formation that binds to human erythrocytes.

Plasmodium falciparum merozoite surface protein (PfMSP) 1 has been studied extensively as a vaccine candidate antigen. PfMSP-1 undergoes proteolytic processing into four major products, such as p83, p30, p38, and p42, that are associated in the form of non-covalent complex(s) with other MSPs. To delineate MSP1 regions involved in the interaction with other MSPs, here we expressed recombinant proteins (PfMSP-1(65)) encompassing part of p38 and p42 regions and PfMSP-1(19). PfMSP-1(65) interacted strongly with PfMSP-3, PfMSP-6, PfMSP-7, and PfMSP-9, whereas PfMSP-1(19) did not interact with any of these proteins. Since MSP-1 complex binds human erythrocytes, we examined the ability of these proteins to bind human erythrocyte. Among the proteins of MSP-1 complex, PfMSP-6 and PfMSP-9 bound to human erythrocytes. Serological studies showed that PfMSP-1(65) was frequently recognized by sera from malaria endemic regions, whereas this was not the case for PfMSP-1(19). In contrast, antibodies against PfMSP-1(19) showed much higher inhibition of merozoite invasion compared with antibodies against the larger PfMSP-1(65) fragment. Importantly, anti-PfMSP-1(19) antibodies recognized both recombinant proteins, PfMSP-1(19) and PfMSP-1(65); however, anti-PfMSP-1(65) antibody failed to recognize the PfMSP-1(19) protein. Taken together, these results demonstrate that PfMSP-1 sequences upstream of the 19 kDa C-terminal region are involved in molecular interactions with other MSPs, and these sequences may probably serve as a smoke screen to evade antibody response to the membrane-bound C-terminal 19 kDa region.