A CONSERVED PARASITE SERINE-PROTEASE PROCESSES THE PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1

The merozoite surface protein-1 of the human malaria parasite Plasmodi um falciparum undergoes an extracellular proteolytic cleavage (seconda ry processing) intrinsic to successful erythrocyte invasion. In the T9 /96 clone of P. falciparum the protease responsible has been character ised as a membrane-associated, calcium-dependent activity, sensitive t o irreversible inhibitors of serine proteases. Here we extend these st udies and show that secondary processing activity in intact merozoites of P. falciparum strains expressing the alternative dimorphic type of merozoite surface protein-1 has identical characteristics, and that t he cleavage site is close to or identical to that in the protein from T9/96. The protease responsible is shown to be parasite-derived, and a ble to catalyse processing of native substrate only when present in th e same membrane. Cleavage of the substrate follows apparent first orde r kinetics for at least 2 half-lives. It is concluded that secondary p rocessing of both dimorphic forms of the P. falciparum merozoite surfa ce protein-1 is a conserved event, mediated by a mechanistically conse rved protease located on the merozoite surface. These observations pro vide clues to the identity of the protease and show that, irrespective of the dimorphic type, secondary processing results in the same, high ly conserved region of the merozoite surface protein-1 remaining on th e surface of the invading merozoite.