title: A conserved parasite serine protease processes the Plasmodium falciparum merozoite surface protein-1.
abstract: The merozoite surface protein-1 of the human malaria parasite Plasmodium falciparum undergoes an extracellular proteolytic cleavage (secondary processing) intrinsic to successful erythrocyte invasion. In the T9/96 clone of P. falciparum the protease responsible has been characterised as a membrane-associated, calcium-dependent activity, sensitive to irreversible inhibitors of serine proteases. Here we extend these studies 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 the 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 able to catalyse processing of native substrate only when present in the same membrane. Cleavage of the substrate follows apparent first order kinetics for at least 2 half-lives. It is concluded that secondary processing of both dimorphic forms of the P. falciparum merozoite surface protein-1 is a conserved event, mediated by a mechanistically conserved protease located on the merozoite surface. These observations provide clues to the identity of the protease and show that, irrespective of the dimorphic type, secondary processing results in the same, highly conserved region of the merozoite surface protein-1 remaining on the surface of the invading merozoite.
authors.affiliation: Division of Parasitology, National Institute for Medical Research, Mill Hill, London, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Blackman
authors.forename: J A
authors.initials: JA
authors.lastname: Chappel
authors.forename: S
authors.initials: S
authors.lastname: Shai
authors.forename: A A
authors.initials: AA
authors.lastname: Holder
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D017125:Genes, Protozoan; D007700:Kinetics; D020066:Merozoite Surface Protein 1; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D000913:Antibodies, Protozoan; D017931:DNA Primers; D016054:DNA, Protozoan; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases