title: Protein targeting to the malaria parasite plastid.
abstract: The relict plastid, or apicoplast, of the malaria parasite Plasmodium falciparum is an essential organelle and a promising drug target. Most apicoplast proteins are nuclear encoded and post-translationally targeted into the organelle using a bipartite N-terminal extension, consisting of a typical endomembrane signal peptide and a plant-like transit peptide. Apicoplast protein targeting commences through the parasite's secretory pathway. We review recent experimental evidence suggesting that the apicoplast resides in the mainstream endomembrane system proximal to the Golgi. Further, we explore possible mechanisms for translocation of nuclear-encoded apicoplast proteins across the four bounding membranes. Recent insights into the composition of the transit peptide and how it is cleaved and degraded after use are also examined. Characterization of apicoplast targeting has not only shed light on how this group of parasites mediate intracellular protein trafficking events but also it has helped identify new targets for therapeutics. The distinctive leader sequences of apicoplast proteins make them readily identifiable, allowing assembly of a virtual organelle metabolome from the genome. Such analysis has lead to the identification of several biochemical pathways that are absent from the human host and thus represent novel therapeutic targets for parasitic infection.
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3050, Australia.
authors: Christopher J
authors: CJ
authors: Tonkin
authors: Ming
authors: M
authors: Kalanon
authors: Geoffrey I
authors: GI
authors: McFadden
mesh_terms: D000818:Animals; D007425:Intracellular Membranes / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000502:physiology; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000502:physiology*; D018087:Plastids / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000502:physiology; D021381:Protein Transport / Q000502:physiology
chemical_list: D026901:Membrane Transport Proteins; D021382:Protein Sorting Signals