title: Lipid interactions of the malaria antigen merozoite surface protein 2.
abstract: With more than half the world's population living at risk of malaria infection, there is a strong demand for the development of an effective malaria vaccine. One promising vaccine candidate is merozoite surface protein 2 (MSP2), which is among the most abundant antigens of the blood stage of the Plasmodium falciparum parasite. In solution, MSP2 is intrinsically unstructured, but little is known about the conformation of native MSP2, which is GPI-anchored to the merozoite surface, or of the implications of that conformation for the immune response induced by MSP2. Initial NMR studies have shown that MSP2 interacts with lipid micelles through a highly conserved N-terminal domain. We have further developed these findings by investigating how different lipid environments affect the protein structure. All of the tested lipid preparations perturbed only the N-terminal part of MSP2. In DPC micelles this region adopts an α-helical structure which we have characterized in detail. Our findings suggest a possible mechanism by which lipid interactions might modulate immune recognition of the conserved N-terminus of MSP2, potentially explaining the apparent immunodominance of the central variable region of this important malaria antigen.
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
authors: Christopher A
authors: CA
authors: MacRaild
authors: Marie Ø
authors: MØ
authors: Pedersen
authors: Robin F
authors: RF
authors: Anders
authors: Raymond S
authors: RS
authors: Norton
mesh_terms: D000953:Antigens, Protozoan / Q000737:chemistry / Q000378:metabolism*; D050356:Lipid Metabolism; D008823:Micelles; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010963:Plasmodium falciparum / Q000378:metabolism*; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000953:Antigens, Protozoan; D008823:Micelles; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium