Mj. Blackman et al., A CONSERVED PARASITE SERINE-PROTEASE PROCESSES THE PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1, Molecular and biochemical parasitology, 62(1), 1993, pp. 103-114
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.