Dataset Information

Membrane transporters in the relict plastid of malaria parasites.

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.

SUBMITTER: Mullin KA

PROVIDER: S-EPMC1480448 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Membrane transporters in the relict plastid of malaria parasites.

Mullin Kylie A KA Lim Liting L Ralph Stuart A SA Spurck Timothy P TP Handman Emanuela E McFadden Geoffrey I GI

Proceedings of the National Academy of Sciences of the United States of America 20060607 25

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 ...[more]

PMID: 16760253

Similar Datasets

Project description:Plasmodium parasites and related apicomplexans contain an essential "complex plastid" organelle of secondary endosymbiotic origin, the apicoplast. Biogenesis of this complex plastid poses a unique challenge requiring evolution of new cellular machinery. We previously conducted a mutagenesis screen for essential apicoplast biogenesis genes to discover organellar pathways with evolutionary and biomedical significance. Here we validate and characterize a gene candidate from our screen, Pf3D7_0913500. Using a conditional knockdown strain, we show that Pf3D7_0913500 depletion causes growth inhibition that is rescued by the sole essential product of the apicoplast, isopentenyl pyrophosphate (IPP), and results in apicoplast loss. Because Pf3D7_0913500 had no previous functional annotation, we name it apicoplast-minus IPP-rescued 4 (AMR4). AMR4 has an annotated CaaX protease and bacteriocin processing (CPBP) domain, which in eukaryotes typically indicates a role in CaaX postprenylation processing. Indeed, AMR4 is the only putative CaaX-like protease in Plasmodium parasites which are known to require protein prenylation, and we confirm that the conserved catalytic residue of AMR4 (E352) is required for its apicoplast function. However, we unexpectedly find that AMR4 does not act in a CaaX postprenylation processing pathway in Plasmodium falciparum Instead, we find that AMR4 is imported into the apicoplast and is derived from a cyanobacterial CPBP gene which was retained through both primary and secondary endosymbiosis. Our findings suggest that AMR4 is not a true CaaX protease, but instead it performs a conserved, uncharacterized chloroplast function that has been retained for complex plastid biogenesis.IMPORTANCEPlasmodium parasites, which cause malaria, and related apicomplexans are important human and veterinary pathogens. These parasites represent a highly divergent and understudied branch of eukaryotes, and as such often defy the expectations set by model organisms. One striking example of unique apicomplexan biology is the apicoplast, an essential but nonphotosynthetic plastid derived from an unusual secondary (eukaryote-eukaryote) endosymbiosis. Endosymbioses are a major driver of cellular innovation, and apicoplast biogenesis pathways represent a hot spot for molecular evolution. We previously conducted an unbiased screen for apicoplast biogenesis genes in P. falciparum to uncover these essential and innovative pathways. Here, we validate a novel gene candidate from our screen and show that its role in apicoplast biogenesis does not match its functional annotation predicted by model eukaryotes. Our findings suggest that an uncharacterized chloroplast maintenance pathway has been reused for complex plastid biogenesis in this divergent branch of pathogens.

Dataset Information

Membrane transporters in the relict plastid of malaria parasites.

Publications

Membrane transporters in the relict plastid of malaria parasites.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets