Membrane-associated proteases process Plasmodium falciparum merozoite surface antigen-1 (MSA1) to fragment gp41.
The Plasmodium falciparum merozoite surface antigen-1 (MSA1) undergoes stage-specific processing; this processing appears isolate-specific during cleavage to fragment gp41. Recombinant substrates were prepared from the two allelic forms of MSA1; the MAD20 substrate was cleaved at four sites in the molecule whilst the K1 form was cleaved once. However both parasite isolates, although expressing different allelic forms of MSA1, possess the same repertoire of MSA1-specific proteases. The cleavage site in native gp41 is conserved between P. falciparum isolates. The specificity of substrate cleavage was determined by N-terminal sequencing of cleaved substrate fragments; two cleavage sites, identical to native MAD20 processed fragments, were not conserved between alleles. An additional non-conserved site was cleaved by an erythrocyte protease. The MSA1-specific proteases were membrane-associated but soluble forms were purified by anion-exchange chromatography. The gp41-specific protease activity was inhibited by serine, thiol and metalloprotease inhibitors whilst the two other MSA1-specific proteases were serine proteases (as was the erythrocyte protease).
Cooper
J A
JA
Zentrum für Molekulare Biologie, Universität Heidelberg, Germany.
Bujard
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D010450:Endopeptidases / Q000378:metabolism; D020066:Merozoite Surface Protein 1; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
D000953:Antigens, Protozoan; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011498:Protein Precursors; D015800:Protozoan Proteins; D010450:Endopeptidases