Structural studies on Plasmodium vivax merozoite surface protein-1

Plasmodium vivax infection is the second most common cause of malaria throughout the world. Like other Plasmodium species, P. vivax has a large protein complex, MSP-1, located on the merozoite surface. The C-terminal MSP-1 sub-unit, MSP-142, is cleaved during red blood cell invasion, causing the majority of the complex to be shed and leaving only a small 15kDa sub-unit, MSP-119, on the merozite surface. MSP-119 is considered a strong vaccine candidate. We have determined the solution structure of MSP-119 from P. vivax using nuclear magnetic resonance (NMR) and show that, like in other Plasmodium species, it consists of two EGF-like domains that are oriented head-to-tail. The protein has a flat, disk-like shape with a highly charged surface. When MSP-119 is part of the larger MSP-142 precursor it exists as an independent domain with no stable contacts to the rest of the sub-unit. Gel filtration and analytical ultracentrifugation experiments indicate that P. vivax MSP-142 exists as a dimer in solution. MSP-119 itself is a monomer, however, 35 amino-acids immediately upstream of its N-terminus are sufficient to cause dimerization. Our data suggest that if MSP-142 exists as a dimer in vivo, secondary processing would cause the dissociation of two tightly linked MSP-119 proteins on the merozoite surface just prior to invasion.