TRG_Pf-PMV_PEXEL_1

The Apicomplexa phylum is comprised of unicellular eukaryotes, which are parasitic agents of various diseases in humans as well as in wild and domesticated animals. Among the most studied Apicomplexa species are the ones belonging to the genera Plasmodium, Toxoplasma, Babesia, Eimeria, Theileria and Sarcocystis (Arisue,2015). Infection of most Apicomplexa is characterized by an apical complex specialisation, substrate-dependent Glideosome mobility, the formation of a parasitophorous vacuole (PV) from the invagination of host cells, and a multicomponent secretory system (White,2018). From the non-fusogenic PV these parasites are able to sequester nutrients and hijack their hosts’ molecular pathways in order to evade immune responses and clearance, remodel the cytoplasm and proliferate. These alterations are achieved by the coordinated export of parasite proteins into the host (Marti,2013).
The Plasmodium Export element (PEXEL) is the best studied trafficking motif in the Apicomplexan phylum and aids species of the Plasmodium parasites to mediate protein export. PEXEL has a dual function, as a cleavage motif recognised by the aspartyl protease Plasmepsin V and as a targeting motif to export processed proteins from the Endoplasmic Reticulum (ER) through the parasite and PV membranes into the infected cell cytosol (de Koning-Ward,2016) (Marti,2013). These proteins are often part of multi-copy gene families such as RIFINs (repetitive interspersed family) and STEVORs (subtelomeric variable open reading frames), but there are also more unique exported proteins (Pick,2011). In Plasmodium falciparum, the most lethal species for humans, PEXEL is present in around 400 exported proteins, representing ~8% of the parasite’s proteome, or ~80% of its exportome, from which 20% are predicted to be essential (de Koning-Ward,2016). The rest of the exported proteins which lack conserved elements are termed PEXEL-negative proteins (PNEPs). It has been proposed that they might associate with other proteins that contain PEXEL in order to be exported (Kumar,2018).
Other Plasmodium species have somewhat more divergent and flexible PEXEL motifs which have not been annotated yet. The Toxoplasma gondii trafficking and cleavage motif, TEXEL, is typically RRL; it is not yet in ELM.