title: Distinct protein classes including novel merozoite surface antigens in Raft-like membranes of Plasmodium falciparum.
abstract: Glycosylphosphatidylinositol (GPI)-anchored proteins coat the surface of extracellular Plasmodium falciparum merozoites, of which several are highly validated candidates for inclusion in a blood-stage malaria vaccine. Here we determined the proteome of gradient-purified detergent-resistant membranes of mature blood-stage parasites and found that these membranes are greatly enriched in GPI-anchored proteins and their putative interacting partners. Also prominent in detergent-resistant membranes are apical organelle (rhoptry), multimembrane-spanning, and proteins destined for export into the host erythrocyte cytosol. Four new GPI-anchored proteins were identified, and a number of other novel proteins that are predicted to localize to the merozoite surface and/or apical organelles were detected. Three of the putative surface proteins possessed six-cysteine (Cys6) motifs, a distinct fold found in adhesive surface proteins expressed in other life stages. All three Cys6 proteins, termed Pf12, Pf38, and Pf41, were validated as merozoite surface antigens recognized strongly by antibodies present in naturally infected individuals. In addition to the merozoite surface, Pf38 was particularly prominent in the secretory apical organelles. A different cysteine-rich putative GPI-anchored protein, Pf92, was also localized to the merozoite surface. This insight into merozoite surfaces provides new opportunities for understanding both erythrocyte invasion and anti-parasite immunity.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050 Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanders
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gilson
authors.forename: Greg T
authors.initials: GT
authors.lastname: Cantin
authors.forename: Doron C
authors.initials: DC
authors.lastname: Greenbaum
authors.forename: Thomas
authors.initials: T
authors.lastname: Nebl
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Carucci
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: McConville
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hodder
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000378:metabolism; D000954:Antigens, Surface / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D003902:Detergents / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D020066:Merozoite Surface Protein 1 / Q000737:chemistry*; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins; D040901:Proteomics; D015800:Protozoan Proteins / Q000737:chemistry
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D003902:Detergents; D017261:Glycosylphosphatidylinositols; D020066:Merozoite Surface Protein 1; C507527:Pf12 antigen, Plasmodium falciparum; C507528:Pf38 antigen, Plasmodium falciparum; C507529:Pf41 antigen, Plasmodium falciparum; D011506:Proteins; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor; D003545:Cysteine