Protein–protein interaction studies reveal the Plasmodium falciparum merozoite surface protein-1 region involved in a complex formation that binds to human erythrocytes

Plasmodium  falciparum Merozoite surface protein (MSP) 1 has been studied extensively as a vaccine candidate antigen. PfMSP-1 undergoes proteolytic processing into four major products; p83, p30, p38 and p42 that are associated in the form of non-covalent complex(s) with other merozoite surface proteins. 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, 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 to antibodies against the larger PfMSP-1 65 fragment. Importantly, anti-PfMSP-1 19 antibodies recognized both recombinant proteins; PfMSP-1 19 as well as PfMSP-1 65 , however anti-PfMSP-1 65 antibody failed to recognize the PfMSP-1 19  protein. Together these results demonstrate that PfMSP-1 sequences upstream of the 19kDa C-terminal region is involved in molecular interactions with other merozoite surface proteins and these sequences may probably serve as a smoke screen to evade antibody response to the membrane bound C-terminal 19 kDa region.