A subtilisin-like protein in secretory organelles of Plasmodium falciparum merozoites.
In the vertebrate host, the malaria parasite invades and replicates asexually within circulating erythrocytes. Parasite proteolytic enzymes play an essential but poorly understood role in erythrocyte invasion. We have identified a Plasmodium falciparum gene, denoted pfsub-1, encoding a member of the subtilisin-like serine protease family (subtilases). The pfsub-1 gene is expressed in asexual blood stages of P. falciparum, and the primary gene product (PfSUB-1) undergoes post-translational processing during secretory transport in a manner consistent with its being converted to a mature, enzymatically active form, as documented for other subtilases. In the invasive merozoite, the putative mature protease (p47) is concentrated in dense granules, which are secretory organelles located toward the apical end of the merozoite. At some point following merozoite release and completion of erythrocyte invasion, p47 is secreted from the parasite in a truncated, soluble form. The subcellular location and timing of secretion of p47 suggest that it is likely to play a role in erythrocyte invasion. PfSUB-1 is a new potential target for antimalarial drug development.
Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom. mblackm@nimr.mrc.ac.uk
M J
MJ
Blackman
H
H
Fujioka
W H
WH
Stafford
M
M
Sajid
B
B
Clough
S L
SL
Fleck
M
M
Aikawa
M
M
Grainger
F
F
Hackett
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002451:Cell Compartmentation; D002454:Cell Differentiation; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000201:enzymology*; D004926:Escherichia coli / Q000235:genetics; D018628:Gene Dosage; D015870:Gene Expression; D017125:Genes, Protozoan; D008969:Molecular Sequence Data; D015388:Organelles / Q000201:enzymology*; D010449:Peptide Mapping; D010963:Plasmodium falciparum / Q000166:cytology / Q000235:genetics* / Q000472:pathogenicity; D016133:Polymerase Chain Reaction; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013381:Subtilisins / Q000096:biosynthesis / Q000235:genetics*
D011993:Recombinant Fusion Proteins; D013381:Subtilisins