Proteolysis of Plasmodium falciparum surface antigen, Pfs230, during gametogenesis

During Plasmodium falciparum gametogenesis, proteolysis of Pfs230, a 360 kD a gametocyte surface protein, generates two large polypeptides, 307 and 300 kDa, that remain associated with the surface of the newly formed gamete. U sing peptide specific antibodies. the amino termini of the 307 and 300 kDa forms have been mapped to between aa 477-487 and aa 523-555, respectively. which is the region between the glutamate rich repeats and the cysteine mot if domains. Concomitantly. two peptides, 47 and 35 kDa, corresponding to th e region upstream from the cleavage site are released into the medium. The membrane permeant cysteine protease inhibitor, E64d, blocks production of t he 300 and 35 kDa forms of Pfs230. but does not alter the formation of the 307 or 47 kDa forms. In contrast, E64, which has been shown to inhibit the development of P. falciparum trophozoites, does not block proteolytic proce ssing of Pfs230. Production of both the 307 and 300 kDa forms was reduced b y a metallo-protease inhibitor, 1,10-phenanthroline. whereas the rest of th e protease inhibitors rested had no effect on Pfs230 processing. This is th e first study of proteolysis during gametogenesis and it demonstrates that the two large forms of Pfs230 produced ale generated by proteases with diff erent specificities. The data also suggest that Pfs230 undergoes proteolyti c processing prior to emergence from the red blood cell. (C) 2000 Elsevier Science B.V. All rights reserved.