title: Proteome analysis reveals a large merozoite surface protein-1 associated complex on the Plasmodium falciparum merozoite surface.
abstract: Plasmodium merozoite surface protein-1 (MSP-1) is an essential antigen for the merozoite invasion of erythrocytes. A key challenge to the development of an effective malaria vaccine that can block the erythrocyte invasion is to establish the molecular interaction(s) among the parasite surface proteins as well as with the host cell encoded receptors. In the present study, we applied molecular interactions and proteome approaches to identify PfMSP-1 associated complex on the merozoite surface. Proteomic analysis identified a major malaria surface protein, PfRhopH3 interacting with PfMSP-1(42). Pull-down experiments with merozoite lysate using anti-PfMSP-1 or anti-PfRhopH3 antibodies showed 16 bands that when identified by tandem mass spectrometry corresponded to11 parasite proteins: PfMSP-3, PfMSP-6, PfMSP-7, PfMSP-9, PfRhopH3, PfRhopH1, PfRAP-1, PfRAP-2, and two RAP domain containing proteins. This MSP-1 associated complex was specifically seen at schizont/merozoite stages but not the next ring stage. We could also identify many of these proteins in culture supernatant, suggesting the shedding of the complex. Interestingly, the PfRhopH3 protein also showed binding to the human erythrocyte and anti-PfRhopH3 antibodies blocked the erythrocyte invasion of the merozoites. These results have potential implications in the development of PfMSP-1 based blood stage malaria vaccine.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Ranjan
authors.forename: Monika
authors.initials: M
authors.lastname: Chugh
authors.forename: Saravanan
authors.initials: S
authors.lastname: Kumar
authors.forename: Shivani
authors.initials: S
authors.lastname: Singh
authors.forename: Shivani
authors.initials: S
authors.lastname: Kanodia
authors.forename: Manzar J
authors.initials: MJ
authors.lastname: Hossain
authors.forename: Reshma
authors.initials: R
authors.lastname: Korde
authors.forename: Amit
authors.initials: A
authors.lastname: Grover
authors.forename: Shikha
authors.initials: S
authors.lastname: Dhawan
authors.forename: Virander S
authors.initials: VS
authors.lastname: Chauhan
authors.forename: Vanga S
authors.initials: VS
authors.lastname: Reddy
authors.forename: Asif
authors.initials: A
authors.lastname: Mohmmed
authors.forename: Pawan
authors.initials: P
authors.lastname: Malhotra
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000378:metabolism; D052940:Merozoites / Q000737:chemistry / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000378:metabolism; D025941:Protein Interaction Mapping; D040901:Proteomics; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D020066:Merozoite Surface Protein 1; D046912:Multiprotein Complexes; D015800:Protozoan Proteins; C065352:rhoptry associated protein, Plasmodium