The malaria parasite exports proteins across its plasma membrane and a surrounding parasitophorous vacuole membrane, into its host erythrocyte. Most exported proteins contain a Host Targeting motif (HT motif) that targets them for export. In the parasite secretory pathway, the HT motif is cleaved by the protease plasmepsin V, but the role of the newly generated N-terminal sequence in protein export is unclear. Using a model protein that is cleaved by an exogenous viral protease, we show that the new N-terminal sequence, normally generated by plasmepsin V cleavage, is sufficient to target a protein for export, and that cleavage by plasmepsin V is not coupled directly to the transfer of a protein to the next component in the export pathway. Mutation of the fourth and fifth positions of the HT motif, as well as amino acids further downstream, block or affect the efficiency of protein export indicating that this region is necessary for efficient export. We also show that the fifth position of the HT motif is important for plasmepsin V cleavage. Our results indicate that plasmepsin V cleavage is required to generate a new N-terminal sequence that is necessary and sufficient to mediate protein export by the malaria parasite.
Protist mitochondrial genomes show a very wide range of gene content, ranging from three genes for respiratory chain components in Apicomplexa and dinoflagellates to nearly 100 genes in
Reclinomonas americana
. In many organisms the rRNA genes are fragmented, although still functional. Some protist mitochondria encode a full set of tRNAs, while others rely on imported molecules. There is similarly a wide variation in mitochondrial genome organization, even among closely related groups. Mitochondrial gene expression and control are generally poorly characterized. Transcription probably relies on a ‘viral-type’ RNA polymerase, although a ‘bacterial-type’ enzyme may be involved in some cases. Transcripts are heavily edited in many lineages. The chloroplast genome generally shows less variation in gene content and organization, although greatly reduced genomes are found in dinoflagellate algae and non-photosynthetic organisms. Genes in the former are located on small plasmids in contrast to the larger molecules found elsewhere. Control of gene expression in chloroplasts involves transcriptional and post-transcriptional regulation. Redox poise and the ATP/ADP ratio are likely to be important determinants. Some protists have an additional extranuclear genome, the nucleomorph, which is a remnant nucleus. Nucleomorphs of two separate lineages have a number of features in common.
Graphical abstractThe extended PRESAN domain is a targeting domain used by multiple Plasmodium species to target PHISTb proteins to the cytoskeleton/plasma membrane of infected cells.
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