MSP2, an abundant GPI-anchored protein found on the surface of Plasmodium falciparum merozoites, is considered a potential component of a malaria vaccine. MSP2 comprises conserved N- and C- terminal regions flanking a central polymorphic region containing repetitive and non-repetitive sequences. The function of MSP2 is unknown but it is carried in to the host erythrocyte on the surface of the invading merozoite where it is rapidly degraded.

Like many malaria antigens, MSP2 is intrinsically unstructured, with few regions of limited conformational restriction in solution.¹ The central variable region appears to dominate natural and protective immune responses; the mechanism by which the conserved regions apparently evade immune surveillance is unclear. More generally, the structural basis and functional significance of immune interactions with unstructured proteins are poorly understood. Analyses using a panel of monoclonal antibodies indicate that parasite MSP2 is antigenically distinct from recombinant MSP2, implying that the conformation of the protein on the parasite surface differs from that in solution. This results in preferential exposure of the highly variable central region of MSP2 on the merozoite surface.² One of the regions that displays some helical propensity in solution is in the short conserved N-terminal sequence. This region interacts with lipid surfaces, stabilizing the helical conformation of this region.³ This suggests a possible mechanism by which lipid interactions might modulate immune recognition of the conserved N-terminus of MSP2.

A more detailed understanding of the conformational differences between parasite and recombinant MSP2 will allow the optimization of MSP2 as a malaria vaccine component.