title: Recycling factors for ribosome disassembly in the apicoplast and mitochondrion of Plasmodium falciparum.
abstract: The reduced genomes of the apicoplast and mitochondrion of the malaria parasite Plasmodium falciparum are actively translated and antibiotic-mediated translation inhibition is detrimental to parasite survival. In order to understand recycling of organellar ribosomes, a critical step in protein translation, we identified ribosome recycling factors (RRF) encoded by the parasite nuclear genome. Targeting of PfRRF1 and PfRRF2 to the apicoplast and mitochondrion respectively was established by localization of leader sequence-GFP fusions. Unlike any RRF characterized thus far, PfRRF2 formed dimers with disulphide interaction(s) and additionally localized in the cytoplasm, thus suggesting adjunct functions for the factor. PfRRF1 carries a large 108-amino-acid insertion in the functionally critical hinge region between the head and tail domains of the protein, yet complemented Escherichia coli RRF in the LJ14frr(ts) mutant and disassembled surrogate E. coli 70S ribosomes in the presence of apicoplast-targeted EF-G. Recombinant PfRRF2 bound E. coli ribosomes and could split monosomes in the presence of the relevant mitochondrial EF-G but failed to complement the LJ14frr(ts) mutant. Although proteins comprising subunits of P. falciparum organellar ribosomes are predicted to differ from bacterial and mitoribosomal counterparts, our results indicate that the essential interactions required for recycling are conserved in parasite organelles.
authors.affiliation: Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Gupta
authors.forename: Snober S
authors.initials: SS
authors.lastname: Mir
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Jackson
authors.forename: Erin E
authors.initials: EE
authors.lastname: Lim
authors.forename: Priyanka
authors.initials: P
authors.lastname: Shah
authors.forename: Ashima
authors.initials: A
authors.lastname: Sinha
authors.forename: Mohammad Imran
authors.initials: MI
authors.lastname: Siddiqi
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Ralph
authors.forename: Saman
authors.initials: S
authors.lastname: Habib
mesh_terms: D000595:Amino Acid Sequence; D063546:Apicoplasts / Q000201:enzymology* / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics*; D014176:Protein Biosynthesis; D055503:Protein Multimerization; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D012333:RNA, Messenger; D012269:Ribosomal Proteins; C087267:ribosome releasing factor