title: Truncation of merozoite surface protein 3 disrupts its trafficking and that of acidic-basic repeat protein to the surface of Plasmodium falciparum merozoites.
abstract: Merozoite surface protein 3 (MSP3), an important vaccine candidate, is a soluble polymorphic antigen associated with the surface of Plasmodium falciparum merozoites. The MSP3 sequence contains three blocks of heptad repeats that are consistent with the formation of an intramolecular coiled-coil. MSP3 also contains a glutamic acid-rich region and a putative leucine zipper sequence at the C-terminus. We have disrupted the msp3 gene by homologous recombination, resulting in the expression of a truncated form of MSP3 that lacks the putative leucine zipper sequence but retains the glutamic acid-rich region and the heptad repeats. Here, we show that truncated MSP3, lacking the putative leucine zipper region, does not localize to the parasitophorous vacuole or interact with the merozoite surface. Furthermore, the acidic-basic repeat antigen (ABRA), which is present on the merozoite surface, also was not localized to the merozoite surface in parasites expressing the truncated form of MSP3. The P. falciparum merozoites lacking MSP3 and ABRA on the surface show reduced invasion into erythrocytes. These results suggest that MSP3 is not absolutely essential for blood stage growth and that the putative leucine zipper region is required for the trafficking of both MSP3 and ABRA to the parasitophorous vacuole.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia.
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Mills
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Pearce
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D018390:Gene Targeting; D017125:Genes, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014617:Vacuoles / Q000469:parasitology*
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D015800:Protozoan Proteins; C089133:merozoite surface protein 3, Plasmodium