title: Targeting and function of proteins mediating translation initiation in organelles of Plasmodium falciparum.
abstract: The malaria parasite Plasmodium falciparum has two translationally active organelles - the apicoplast and mitochondrion, which import nuclear-encoded translation factors to mediate protein synthesis. Initiation of translation is a complex step wherein initiation factors (IFs) act in a regulated manner to form an initiation complex. We identified putative organellar IFs and investigated the targeting, structure and function of IF1, IF2 and IF3 homologues encoded by the parasite nuclear genome. A single PfIF1 is targeted to the apicoplast. Apart from its critical ribosomal interactions, PfIF1 also exhibited nucleic-acid binding and melting activities and mediated transcription anti-termination. This suggests a prominent ancillary function for PfIF1 in destabilisation of DNA and RNA hairpin loops encountered during transcription and translation of the A+T rich apicoplast genome. Of the three putative IF2 homologues, only one (PfIF2a) was an organellar protein with mitochondrial localisation. We additionally identified an IF3 (PfIF3a) that localised exclusively to the mitochondrion and another protein, PfIF3b, that was apicoplast targeted. PfIF3a exhibited ribosome anti-association activity, and monosome splitting by PfIF3a was enhanced by ribosome recycling factor (PfRRF2) and PfEF-G(Mit). These results fill a gap in our understanding of organellar translation in Plasmodium, which is the site of action of several anti-malarial compounds.
authors.affiliation: Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Afreen
authors.initials: A
authors.lastname: Haider
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., 3010, Australia.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Allen
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., 3010, Australia.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Jackson
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Vic., 3010, Australia.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Ralph
authors.affiliation: Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Saman
authors.initials: S
authors.lastname: Habib
mesh_terms: D063546:Apicoplasts / Q000235:genetics* / Q000378:metabolism; D015977:Eukaryotic Initiation Factor-1 / Q000235:genetics / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D015977:Eukaryotic Initiation Factor-1; D015852:Eukaryotic Initiation Factor-2; D039621:Eukaryotic Initiation Factor-3; D015800:Protozoan Proteins; D012269:Ribosomal Proteins; C087267:ribosome releasing factor