Targeting malaria virulence and remodeling proteins to the host erythrocyte.
To establish infection in the host, malaria parasites export remodeling and virulence proteins into the erythrocyte. These proteins can traverse a series of membranes, including the parasite membrane, the parasitophorous vacuole membrane, and the erythrocyte membrane. We show that a conserved pentameric sequence plays a central role in protein export into the host cell and predict the exported proteome in Plasmodium falciparum. We identified 400 putative erythrocyte-targeted proteins corresponding to approximately 8% of all predicted genes, with 225 virulence proteins and a further 160 proteins likely to be involved in remodeling of the host erythrocyte. The conservation of this signal across Plasmodium species has implications for the development of new antimalarials.
Marti
Matthias
M
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
Good
Robert T
RT
Rug
Melanie
M
Knuepfer
Ellen
E
Cowman
Alan F
AF
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D003593:Cytoplasm / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D020869:Gene Expression Profiling; D017125:Genes, Protozoan; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D016778:Malaria, Falciparum / Q000469:parasitology; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010961:Plasmodium / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D021382:Protein Sorting Signals; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors