title: Processing of an apicoplast leader sequence in Plasmodium falciparum and the identification of a putative leader cleavage enzyme.
abstract: The plastid (apicoplast) of the malaria-causing parasite Plasmodium falciparum was derived via a secondary endosymbiotic process. As in other secondary endosymbionts, numerous genes for apicoplast proteins are located in the nucleus, and the encoded proteins are targeted to the organelle courtesy of a bipartite N-terminal extension. The first part of this leader sequence is a signal peptide that targets proteins to the secretory pathway. The second, so-called transit peptide region is required to direct proteins from the secretory pathway across the multiple membranes surrounding the apicoplast. In this paper we perform a pulse-chase experiment and N-terminal sequencing to show that the transit peptide of an apicoplast-targeted protein is cleaved, presumably upon import of the protein into the apicoplast. We identify a gene whose product likely performs this cleavage reaction, namely a stromal-processing peptidase (SPP) homologue. In plants SPP cleaves the transit peptides of plastid-targeted proteins. The P. falciparum SPP homologue contains a bipartite N-terminal apicoplast-targeting leader. Interestingly, it shares this leader sequence with a Delta-aminolevulinic acid dehydratase homologue via an alternative splicing event.
authors.affiliation: Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Melboure 3010, Australia.
authors.forename: Giel G
authors.initials: GG
authors.lastname: van Dooren
authors.forename: Vanessa
authors.initials: V
authors.lastname: Su
authors.forename: Marthe C
authors.initials: MC
authors.lastname: D'Ombrain
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: McFadden
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D006418:Heme / Q000096:biosynthesis; D008666:Metalloendopeptidases / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D010940:Plant Proteins; D010963:Plasmodium falciparum / Q000737:chemistry*; D000623:Porphobilinogen Synthase / Q000235:genetics / Q000502:physiology; D021382:Protein Sorting Signals; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010940:Plant Proteins; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; D006418:Heme; D008666:Metalloendopeptidases; C071986:stromal processing peptidase; D000623:Porphobilinogen Synthase