title: Biochemical and functional analysis of two Plasmodium falciparum blood-stage 6-cys proteins: P12 and P41.
abstract: The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here we investigate the biochemical nature and function of two blood-stage 6-cys proteins in Plasmodium falciparum, the most pathogenic species to afflict humans. We show that native P12 and P41 form a stable heterodimer on the infective merozoite surface and are secreted following invasion, but could find no evidence that this complex mediates erythrocyte-receptor binding. That P12 and P41 do not appear to have a major role as adhesins to erythrocyte receptors was supported by the observation that antisera to these proteins did not substantially inhibit erythrocyte invasion. To investigate other functional roles for these proteins their genes were successfully disrupted in P. falciparum, however P12 and P41 knockout parasites grew at normal rates in vitro and displayed no other obvious phenotypic changes. It now appears likely that these blood-stage 6-cys proteins operate as a pair and play redundant roles either in erythrocyte invasion or in host-immune interactions.
authors: Burnet Institute, Melbourne, Victoria, Australia.
authors: Tana
authors: T
authors: Taechalertpaisarn
authors: Cecile
authors: C
authors: Crosnier
authors: S Josefin
authors: SJ
authors: Bartholdson
authors: Anthony N
authors: AN
authors: Hodder
authors: Jenny
authors: J
authors: Thompson
authors: Leyla Y
authors: LY
authors: Bustamante
authors: Danny W
authors: DW
authors: Wilson
authors: Paul R
authors: PR
authors: Sanders
authors: Gavin J
authors: GJ
authors: Wright
authors: Julian C
authors: JC
authors: Rayner
authors: Alan F
authors: AF
authors: Cowman
authors: Paul R
authors: PR
authors: Gilson
authors: Brendan S
authors: BS
authors: Crabb
mesh_terms: D000913:Antibodies, Protozoan / Q000276:immunology; D017077:Culture Media, Conditioned / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D004926:Escherichia coli / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D052940:Merozoites / Q000378:metabolism; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000913:Antibodies, Protozoan; D017077:Culture Media, Conditioned; D015800:Protozoan Proteins; D011994:Recombinant Proteins