Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum.
Merozoites of the malaria parasite Plasmodium falciparum expose at their surface a large multiprotein complex, composed of proteolytically processed, noncovalently associated products of at least three genes, msp-1, msp-6, and msp-7. During invasion of erythrocytes, this complex is shed from the surface except for a small glycosylphosphatidylinositol-anchored portion originating from MSP-1. The proteolytic cleavage separating the C-terminal portion of MSP-1 is required for successful invasion. Little is known about the structure and function of the abundant and essential multipartite complex. Using heterologously produced MSP-1, MSP-6, and MSP-7 in precursor and with the exception of MSP-7 in processed form, we have studied in vitro the complex formation between the different proteins to identify the interaction partners within the complex. Both MSP-6(36) and MSP-7 bind only to MSP-1 subunits that are shed, but although MSP-6(36) contacts just subunit p38, MSP-7 interacts with p83, p30, and p38. The intact C-terminal region of MSP-6 is required for the association with p38 as well as for its multimerization into tetramers. Furthermore, our data suggest that only the processed form and not the precursor form of MSP-1 interacts with MSP-6(36). MSP-6- as well as MSP-7-specific rabbit antibodies inhibit parasite multiplication in vitro as shown previously for antibodies directed against MSP-1. Our findings raise interesting questions with regard to proteolysis-mediated mechanisms of maturation of the MSP-1-MSP-6-MSP-7 complex and to the mode by which antibodies directed against this complex interfere with parasite multiplication.
Kauth
Christian W
CW
Zentrum fuer Molekulare Biologie der Universitaet Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Woehlbier
Ute
U
Kern
Michaela
M
Mekonnen
Zeleke
Z
Lutz
Rolf
R
Mücke
Norbert
N
Langowski
Jörg
J
Bujard
Hermann
H
D000818:Animals; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005434:Flow Cytometry; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D020066:Merozoite Surface Protein 1 / Q000737:chemistry*; D008957:Models, Genetic; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C435213:merozoite surface protein 6, Plasmodium; C439571:merozoite surface protein 7, Plasmodium; D048051:p38 Mitogen-Activated Protein Kinases