Interactions between Merozoite Surface Proteins 1, 6, and 7 of the Malaria Parasite Plasmodium falciparum

• Published in: The Journal of biological chemistry 2006-10, Vol.281 (42), p.31517-31527
• Main Authors: Kauth, Christian W, Woehlbier, Ute, Kern, Michaela, Mekonnen, Zeleke, Lutz, Rolf, Mücke, Norbert, Langowski, Jörg, Bujard, Hermann
• Format: Article
• Language: English
• Subjects: Animals; Cloning, Molecular; Cross-Linking Reagents - pharmacology; Erythrocytes - metabolism; Erythrocytes - parasitology; Flow Cytometry; Humans; Membrane Proteins - chemistry; Merozoite Surface Protein 1 - chemistry; Models, Genetic; p38 Mitogen-Activated Protein Kinases - metabolism; Plasmodium falciparum; Plasmodium falciparum - metabolism; Protein Binding; Protein Conformation; Protozoan Proteins - chemistry
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M604641200

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-6₃₆ and MSP-7 bind only to MSP-1 subunits that are shed, but although MSP-6₃₆ 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-6₃₆. 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.