Cyclosporin-binding proteins of Plasmodium falciparum.
A number of cyclosporins, including certain non-immunosuppressive ones, are potent inhibitors of the intraerythrocytic growth of the human malarial parasite Plasmodium falciparum. The major cyclosporin-binding proteins of P. falciparum were investigated by affinity chromatography on cyclosporin-Affigel followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, Western blotting, and peptide mass fingerprinting. The two bands obtained on gels were shown to correspond to cyclophilins, PfCyP-19A (formerly PfCyP-19) and PfCyP-19B, whose genes had been characterised previously. PfCyP-19B was an abundant protein of intraerythrocytic P. falciparum (up to 0.5% of parasite protein) that was present in the highest amounts in schizont-stage parasites. Unexpectedly, given its apparent signal sequence, it was located primarily in the cytosol of the parasite. The peptidyl-prolyl cis-trans isomerase activity of recombinant PfCyP-19B had the same profile of susceptibility to cyclosporin derivatives as the bulk isomerase activity of crude P. falciparum extracts. The binding of cyclosporins to cyclophilins may be relevant to the mechanism of action of the drug in the parasite.
Gavigan
Clare S
CS
Department of Microbiology, Moyne Institute, Trinity College, Dublin 2, Ireland.
Kiely
Senan P
SP
Hirtzlin
Jocelyne
J
Bell
Angus
A
D000818:Animals; D002846:Chromatography, Affinity; D021983:Cyclophilins / Q000032:analysis* / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D008856:Microscopy, Fluorescence; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D010963:Plasmodium falciparum / Q000737:chemistry*; D013053:Spectrophotometry
D016572:Cyclosporine; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase