Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding

• Published in: Nature communications Vol. 7; no. 1; p. 10470
• Main Authors: Boddey, Justin A., O’Neill, Matthew T., Lopaticki, Sash, Carvalho, Teresa G., Hodder, Anthony N., Nebl, Thomas, Wawra, Stephan, van West, Pieter, Ebrahimzadeh, Zeinab, Richard, Dave, Flemming, Sven, Spielmann, Tobias, Przyborski, Jude, Babon, Jeff J., Cowman, Alan F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 14/63; 631/326/417; 631/45/287/1194; 631/80/2023; 82; 82/103; 82/80; Amino Acid Motifs; Cell Membrane; Endoplasmic reticulum; Escherichia coli; Exports; Humanities and Social Sciences; Hypotheses; Laboratories; Lopinavir - pharmacology; Malaria; multidisciplinary; Parasites; Parasitology; Phosphatidylinositol Phosphates - metabolism; Plasmodium falciparum - genetics; Plasmodium falciparum - metabolism; Protein Binding; Proteins; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Science; Science (multidisciplinary); Australia; Germany
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10470

Plasmodium falciparum
exports proteins into erythrocytes using the
Plasmodium
export element (PEXEL) motif, which is cleaved in the endoplasmic reticulum (ER) by plasmepsin V (PMV). A recent study reported that phosphatidylinositol-3-phosphate (PI(3)P) concentrated in the ER binds to PEXEL motifs and is required for export independent of PMV, and that PEXEL motifs are functionally interchangeable with RxLR motifs of oomycete effectors. Here we show that the PEXEL does not bind PI(3)P, and that this lipid is not concentrated in the ER. We find that RxLR motifs cannot mediate export in
P. falciparum
. Parasites expressing a mutated version of KAHRP, with the PEXEL motif repositioned near the signal sequence, prevented PMV cleavage. This mutant possessed the putative PI(3)P-binding residues but is not exported. Reinstatement of PEXEL to its original location restores processing by PMV and export. These results challenge the PI(3)P hypothesis and provide evidence that PEXEL position is conserved for co-translational processing and export.
Export of
Plasmodium falciparum
proteins into infected erythrocytes relies upon the PEXEL motif in target proteins. Here Boddey
et al.
challenge the hypothesis that the PEXEL motif mediates export by binding PI(3)P and instead suggest it acts via cleavage by plasmepsin V.