title: Plasmodium falciparum subtilisin-like protease 2, a merozoite candidate for the merozoite surface protein 1-42 maturase.
abstract: The process of human erythrocyte invasion by Plasmodium falciparum parasites involves a calcium-dependent serine protease with properties consistent with a subtilisin-like activity. This enzyme achieves the last crucial maturation step of merozoite surface protein 1 (MSP1) necessary for parasite entry into the host erythrocyte. In eukaryotic cells, such processing steps are 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 deduced active site sequence resembles more bacterial subtilisins. Therefore, we propose that PfSUB2 belongs to a subclass of eukaryotic subtilisins different from proprotein convertases. Pfsub2 is expressed during merozoite differentiation and encodes an integral membrane protein localized in the merozoite dense granules, a secretory organelle whose contents are believed to participate in a late step of the erythrocyte invasion. PfSUB2's subcellular localization, 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 drugs.
authors.affiliation: Biology of Host-Parasite Interactions Unit, Unité de Recherche Associée-Centre National de la Recherche Scientifique 1960, Immunology Department, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France. jcb@pasteur.fr
authors.forename: J C
authors.initials: JC
authors.lastname: Barale
authors.forename: T
authors.initials: T
authors.lastname: Blisnick
authors.forename: H
authors.initials: H
authors.lastname: Fujioka
authors.forename: P M
authors.initials: PM
authors.lastname: Alzari
authors.forename: M
authors.initials: M
authors.lastname: Aikawa
authors.forename: C
authors.initials: C
authors.lastname: Braun-Breton
authors.forename: G
authors.initials: G
authors.lastname: Langsley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D020066:Merozoite Surface Protein 1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics* / Q000472:pathogenicity; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013381:Subtilisins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020066:Merozoite Surface Protein 1; D011993:Recombinant Fusion Proteins; D013381:Subtilisins; C119550:sub-2 protein, Plasmodium falciparum