Processing of an Apicoplast Leader Sequence inPlasmodium falciparum and the Identification of a Putative Leader Cleavage Enzyme

• Published in: The Journal of biological chemistry Vol. 277; no. 26; pp. 23612 - 23619
• Main Authors: van Dooren, Giel G., Su, Vanessa, D'Ombrain, Marthe C., McFadden, Geoffrey I.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 28.06.2002; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M201748200

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 Δ-aminolevulinic acid dehydratase homologue via an alternative splicing event.