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dc.contributor.advisorFischer, Karsten
dc.contributor.authorJohnsen, Hanne Risan
dc.date.accessioned2010-03-05T07:54:40Z
dc.date.available2010-03-05T07:54:40Z
dc.date.issued2009-05-15
dc.description.abstractThe apicomplexan parasites including the causative agents of malaria (Plasmodium spp.) and toxoplasmosis (Toxoplasma gondii) are running the risk of developing resistance to existing drugs. Members of the phylum Apicomplexa harbour a relict plastid, the apicoplast, which show homology to the chloroplasts of plants and algae. The apicoplast appears to be indispensable to the parasites, and due to its prokaryotic origin it represents an excellent drug target. T. gondii possesses a single plastidic membrane transporter (TgPT) that shows similarity to the phosphate translocators (pPTs) in higher plants which comprises four subfamilies (TPT, PPT, GPT, XPT). Its physiological function has not been previously studied, but the TgPT was proposed to comprise a connection between the metabolic pathways in the apicoplast and the metabolic processes in the cytosol. In this study, the substrate specificities of the TgPT were determined by heterologous expression of the protein in yeast and reconstitution of its transport activity in liposomes. The TgPT showed similarities to both TPTs and PPTs from higher plants combining the transport activities of the two subfamilies by simultaneously transporting compounds phosphorylated at different C-atoms. The TgPT accepts inorganic phosphate and PEP equally as substrates, having an even higher affinity to triose phosphates and 3-PGA. Based on our results, the TgPT likely connect the cytosolic metabolism with metabolic pathways in the apicoplast by delivering carbon units for at least two essential biosynthetic pathways, the fatty acid synthesis and the DOXP pathway for isoprenoid synthesis. Additionally, the TgPT contributes an indirect supply of ATP and reduction power to the apicoplast. These results have recently been corroborated by Boris Striepen and his group by showing that a knock-out of the TgPT resulted in rapid death of the parasite, establishing the transporter as essential for parasite viability and thereby an attractive drug target.en
dc.format.extent3099485 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10037/2426
dc.identifier.urnURN:NBN:no-uit_munin_2176
dc.language.isoengen
dc.publisherUniversitetet i Tromsøen
dc.publisherUniversity of Tromsøen
dc.rights.accessRightsopenAccess
dc.subject.courseIDBIO-3910nor
dc.subjectVDP::Mathematics and natural science: 400::Zoology and botany: 480::Ecology: 488en
dc.subjectVDP::Agriculture and fishery disciplines: 900::Fisheries science: 920::Resource biology: 921en
dc.subjectApicomplexaen
dc.subjectMembrane transporteren
dc.subjectPhosphate translocatoren
dc.subjectplastidsen
dc.titleThe substrate specificities and physiological function of the Toxoplasma gondii apicoplast phosphate translocatoren
dc.typeMaster thesisen
dc.typeMastergradsoppgaveen


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