Literature DB >> 16760253

Membrane transporters in the relict plastid of malaria parasites.

Kylie A Mullin1, Liting Lim, Stuart A Ralph, Timothy P Spurck, Emanuela Handman, Geoffrey I McFadden.   

Abstract

Malaria parasites contain a nonphotosynthetic plastid homologous to chloroplasts of plants. The parasite plastid synthesizes fatty acids, heme, iron sulfur clusters and isoprenoid precursors and is indispensable, making it an attractive target for antiparasite drugs. How parasite plastid biosynthetic pathways are fuelled in the absence of photosynthetic capture of energy and carbon was not clear. Here, we describe a pair of parasite transporter proteins, PfiTPT and PfoTPT, that are homologues of plant chloroplast innermost membrane transporters responsible for moving phosphorylated C3, C5, and C6 compounds across the plant chloroplast envelope. PfiTPT is shown to be localized in the innermost membrane of the parasite plastid courtesy of a cleavable N-terminal targeting sequence. PfoTPT lacks such a targeting sequence, but is shown to localize in the outermost parasite plastid membrane with its termini projecting into the cytosol. We have identified these membrane proteins in the parasite plastid and determined membrane orientation for PfoTPT. PfiTPT and PfoTPT are proposed to act in tandem to transport phosphorylated C3 compounds from the parasite cytosol into the plastid. Thus, the transporters could shunt glycolytic derivatives of glucose scavenged from the host into the plastid providing carbon, reducing equivalents and ATP to power the organelle.

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Year:  2006        PMID: 16760253      PMCID: PMC1480448          DOI: 10.1073/pnas.0602293103

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  38 in total

Review 1.  Origin, targeting, and function of the apicomplexan plastid.

Authors:  D S Roos; M J Crawford; R G Donald; J C Kissinger; L J Klimczak; B Striepen
Journal:  Curr Opin Microbiol       Date:  1999-08       Impact factor: 7.934

Review 2.  Tropical infectious diseases: metabolic maps and functions of the Plasmodium falciparum apicoplast.

Authors:  Stuart A Ralph; Giel G van Dooren; Ross F Waller; Michael J Crawford; Martin J Fraunholz; Bernardo J Foth; Christopher J Tonkin; David S Roos; Geoffrey I McFadden
Journal:  Nat Rev Microbiol       Date:  2004-03       Impact factor: 60.633

3.  Dissection of brefeldin A-sensitive and -insensitive steps in apicoplast protein targeting.

Authors:  Amy DeRocher; Brian Gilbert; Jean E Feagin; Marilyn Parsons
Journal:  J Cell Sci       Date:  2005-01-18       Impact factor: 5.285

4.  Thermolysin is a suitable protease for probing the surface of intact pea chloroplasts.

Authors:  K Cline; M Werner-Washburne; J Andrews; K Keegstra
Journal:  Plant Physiol       Date:  1984-07       Impact factor: 8.340

5.  A plastid segregation defect in the protozoan parasite Toxoplasma gondii.

Authors:  C Y He; M K Shaw; C H Pletcher; B Striepen; L G Tilney; D S Roos
Journal:  EMBO J       Date:  2001-02-01       Impact factor: 11.598

Review 6.  Fatty Acid synthesis as a target for antimalarial drug discovery.

Authors:  Jeff Zhiqiang Lu; Patricia J Lee; Norman C Waters; Sean T Prigge
Journal:  Comb Chem High Throughput Screen       Date:  2005-02       Impact factor: 1.339

7.  Phase separation of integral membrane proteins in Triton X-114 solution.

Authors:  C Bordier
Journal:  J Biol Chem       Date:  1981-02-25       Impact factor: 5.157

8.  Processing of an apicoplast leader sequence in Plasmodium falciparum and the identification of a putative leader cleavage enzyme.

Authors:  Giel G van Dooren; Vanessa Su; Marthe C D'Ombrain; Geoffrey I McFadden
Journal:  J Biol Chem       Date:  2002-04-25       Impact factor: 5.157

9.  A type II pathway for fatty acid biosynthesis presents drug targets in Plasmodium falciparum.

Authors:  Ross F Waller; Stuart A Ralph; Michael B Reed; Vanessa Su; James D Douglas; David E Minnikin; Alan F Cowman; Gurdyal S Besra; Geoffrey I McFadden
Journal:  Antimicrob Agents Chemother       Date:  2003-01       Impact factor: 5.191

10.  Functional characterization of the acyl carrier protein (PfACP) and beta-ketoacyl ACP synthase III (PfKASIII) from Plasmodium falciparum.

Authors:  Norman C Waters; Karen M Kopydlowski; Tadeusz Guszczynski; Lan Wei; Patrice Sellers; Jill T Ferlan; Patricia J Lee; Zhiyu Li; Cassandra L Woodard; Shamira Shallom; Malcolm J Gardner; Sean T Prigge
Journal:  Mol Biochem Parasitol       Date:  2002-08-28       Impact factor: 1.759

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  50 in total

Review 1.  The apicoplast.

Authors:  Geoffrey Ian McFadden
Journal:  Protoplasma       Date:  2010-12-17       Impact factor: 3.356

Review 2.  Nutrient transport and pathogenesis in selected parasitic protozoa.

Authors:  Scott M Landfear
Journal:  Eukaryot Cell       Date:  2011-01-07

3.  Apicoplast targeting of a Toxoplasma gondii transmembrane protein requires a cytosolic tyrosine-based motif.

Authors:  Amy E DeRocher; Anuradha Karnataki; Pashmi Vaney; Marilyn Parsons
Journal:  Traffic       Date:  2012-02-20       Impact factor: 6.215

Review 4.  More membranes, more proteins: complex protein import mechanisms into secondary plastids.

Authors:  Swati Agrawal; Boris Striepen
Journal:  Protist       Date:  2010-10-30

Review 5.  Protein trafficking to the apicoplast: deciphering the apicomplexan solution to secondary endosymbiosis.

Authors:  Marilyn Parsons; Anuradha Karnataki; Jean E Feagin; Amy DeRocher
Journal:  Eukaryot Cell       Date:  2007-05-18

Review 6.  Make it or take it: fatty acid metabolism of apicomplexan parasites.

Authors:  Jolly Mazumdar; Boris Striepen
Journal:  Eukaryot Cell       Date:  2007-08-22

7.  Apicoplast and mitochondrion in gametocytogenesis of Plasmodium falciparum.

Authors:  Noriko Okamoto; Timothy P Spurck; Christopher D Goodman; Geoffrey I McFadden
Journal:  Eukaryot Cell       Date:  2008-11-07

8.  A thioredoxin family protein of the apicoplast periphery identifies abundant candidate transport vesicles in Toxoplasma gondii.

Authors:  Amy E DeRocher; Isabelle Coppens; Anuradha Karnataki; Luke A Gilbert; Michael E Rome; Jean E Feagin; Peter J Bradley; Marilyn Parsons
Journal:  Eukaryot Cell       Date:  2008-06-27

Review 9.  The malaria parasite Plasmodium falciparum: cell biological peculiarities and nutritional consequences.

Authors:  Stefan Baumeister; Markus Winterberg; Jude M Przyborski; Klaus Lingelbach
Journal:  Protoplasma       Date:  2009-11-25       Impact factor: 3.356

10.  Atypical lipid composition in the purified relict plastid (apicoplast) of malaria parasites.

Authors:  Cyrille Y Botté; Yoshiki Yamaryo-Botté; Thusitha W T Rupasinghe; Kylie A Mullin; James I MacRae; Timothy P Spurck; Ming Kalanon; Melanie J Shears; Ross L Coppel; Paul K Crellin; Eric Maréchal; Malcolm J McConville; Geoffrey I McFadden
Journal:  Proc Natl Acad Sci U S A       Date:  2013-04-15       Impact factor: 11.205

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