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Traffic. 2011 Sep;12(9):1124-38. doi: 10.1111/j.1600-0854.2011.01232.x. Epub 2011 Jul 7.

Plasmodium falciparum apicoplast transit peptides are unstructured in vitro and during apicoplast import.

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1
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Room E5132, 615 North Wolfe Street, Baltimore, MD 21205, USA.

Abstract

Trafficking of soluble proteins to the apicoplast in Plasmodium falciparum is determined by an N-terminal transit peptide (TP) which is necessary and sufficient for apicoplast import. Apicoplast precursor proteins are synthesized at the rough endoplasmic reticulum, but are then specifically sorted from other proteins in the secretory pathway. The mechanism of TP recognition is presently unknown. Apicoplast TPs do not contain a conserved sequence motif; therefore, we asked whether they contain an essential structural motif. Using nuclear magnetic resonance to study a model TP from acyl carrier protein, we found a short, low-occupancy helix, but the TP was otherwise disordered. Using an in vivo localization assay, we blocked TP secondary structure by proline mutagenesis, but found robust apicoplast localization. Alternatively, we increased the helical content of the TP through mutation while maintaining established TP characteristics. Apicoplast import was disrupted in a helical mutant TP, but import was then restored by the further addition of a single proline. We conclude that structure in the TP interferes with apicoplast import, and therefore TPs are functionally disordered. These results provide an explanation for the amino acid bias observed in apicoplast TPs.

PMID:
21668595
PMCID:
PMC3629917
DOI:
10.1111/j.1600-0854.2011.01232.x
[Indexed for MEDLINE]
Free PMC Article
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