title: Cooperative domains define a unique host cell-targeting signal in Plasmodium falciparum-infected erythrocytes.
abstract: When the malaria parasite Plasmodium falciparum infects an erythrocyte, it resides in a parasitophorous vacuole and remarkably exports proteins into the periphery of its host cell. Two of these proteins, the histidine-rich proteins I and II (PfHRPI and PfHRPII), are exported to the erythrocyte cytoplasm. PfHRPI has been linked to cell-surface "knobby" protrusions that mediate cerebral malaria and are a frequent cause of death. PfHRPII has been implicated in (i) the production of hemozoin, the black pigment associated with disease, as well as (ii) interactions with the erythrocyte cytoskeleton. Here we show that a tripartite signal that is comprised of an endoplasmic reticulum-type signal sequence followed by a bipartite vacuolar translocation signal derived from HRPII and HRPI exports GFP from the parasitophorous vacuole to the host cytoplasm. The bipartite vacuolar translocation signal is comprised of unique, peptidic (approximately equal to 40-aa) sequences. A domain within it contains the signal for export to "cleft" transport intermediates in the host erythrocyte and may thereby regulate the pathway of export to the host cytoplasm. A signal for posttranslational, vacuolar exit of proteins has hitherto not been described in eukaryotic secretion.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active; D003593:Cytoplasm / Q000469:parasitology; D016054:DNA, Protozoan / Q000235:genetics; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D066298:In Vitro Techniques; D016778:Malaria, Falciparum / Q000469:parasitology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014617:Vacuoles / Q000469:parasitology; D000099053:Histidine-Rich Glycoprotein
chemical_list: D016054:DNA, Protozoan; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000099053:Histidine-Rich Glycoprotein