Plasmodium falciparum subtilisin-like protease 2, a merozoite candidate for the merozoite surface protein 1-42 maturase

The process of human erythrocyte invasion by Plasmodium falciparum parasite s involves a calcium-dependent serine protease with properties consistent w ith a subtilisin-like activity. This enzyme achieves the last crucial matur ation step of merozoite surface protein 1 (MSP1) necessary for parasite ent ry into the host erythrocyte. In eukaryotic cells, such processing steps ar e performed by subtilisin-like maturases, known as proprotein convertases. In an attempt to characterize the MSP1 maturase, we have identified a gene that encodes a P. falciparum subtilisin-like protease (PfSUB2) whose deduce d active site sequence resembles more bacterial subtilisins. Therefore, we propose that PfSUB2 belongs to a subclass of eukaryotic subtilisins differe nt from proprotein convertases, Pfsub2 is expressed during merozoite differ entiation and encodes an integral membrane protein localized in the merozoi te dense granules, a secretory organelle whose contents are believed to par ticipate in a late step of the erythrocyte invasion. PfSUB2's subcellular l ocalization, together with its predicted enzymatic properties, leads us to propose that PfSUB2 could be responsible for the late MSP1 maturation step and thus is an attractive target for the development of new antimalarial dr ugs.