The crystal structure of C-terminal merozoite surface protein 1 at 1.8 angstrom resolution, a highly protective malaria vaccine candidate

The C-terminal proteolytic processing product of merozoite surface protein 1 (MSP1) appears essential for successful erythrocyte invasion by the malar ial parasite, Plasmodium. We have determined the crystal structure at 1.8 A ngstrom resolution of a soluble baculovirus-recombinant form of the protein from P. cynomolgi, which confers excellent protective efficacy in primate vaccination trials. The structure comprises two EGF-like domains, and seque nce comparisons strongly suggest that the same conformation is present in a ll species of Plasmodium, including P. falciparum and P. vivax, which are p athogenic in man. In particular, conserved interdomain contacts between the two EGF modules should preserve the compact form of the molecule in all sp ecies. Implications of the crystal structure for anti-malarial vaccine deve lopment are discussed.