title: A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites.
abstract: The malaria parasite Plasmodium falciparum faces drastic osmotic changes during kidney passages and is engaged in the massive biosynthesis of glycerolipids during its development in the blood-stage. We identified a single aquaglyceroporin (PfAQP) in the nearly finished genome of P. falciparum with highest similarity to the Escherichia coli glycerol facilitator (50.4%), but both canonical Asn-Pro-Ala (NPA) motifs in the pore region are changed to Asn-Leu-Ala (NLA) and Asn-Pro-Ser (NPS), respectively. Expression in Xenopus oocytes renders them highly permeable for both water and glycerol. Sugar alcohols up to five carbons and urea pass the pore. Mutation analyses of the NLA/NPS motifs showed their structural importance, but the symmetrical pore properties were maintained. PfAQP is expressed in blood-stage parasites throughout the development from rings via trophozoites to schizonts and is localized to the parasite but not to the erythrocyte cytoplasm or membrane. Its unique bi-functionality indicates functions in the protection from osmotic stress and efficiently provides access to the serum glycerol pool for the use in ATP generation and primarily in the phospholipid synthesis.
authors.affiliation: Department of Pharmaceutical Biochemistry, University of Tübingen, Morgenstelle 8, Tübingen D-72076, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hansen
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Schultz
authors.forename: Eric
authors.initials: E
authors.lastname: Beitz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D016678:Genome; D005990:Glycerol / Q000737:chemistry; D005994:Glycerophosphates / Q000378:metabolism; D006019:Glycolysis; D008055:Lipids / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D009995:Osmosis; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000378:metabolism*; D018272:Porins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D018075:RNA, Complementary / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014867:Water / Q000737:chemistry; D014981:Xenopus
chemical_list: D005994:Glycerophosphates; D008055:Lipids; C449801:PfAQP protein, Plasmodium falciparum; D018272:Porins; D015800:Protozoan Proteins; D018075:RNA, Complementary; D014867:Water; D000255:Adenosine Triphosphate; C029620:alpha-glycerophosphoric acid; D005990:Glycerol