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

Nature Communications
Justin A BoddeyAlan F Cowman

Abstract

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.

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Citations

Jul 5, 2016·Nature Reviews. Microbiology·Tania F de Koning-WardPaul R Gilson
Jan 10, 2017·Cellular Microbiology·Natalie J SpillmanDaniel E Goldberg
Mar 29, 2016·Current Opinion in Cell Biology·Michael J CoffeyJustin A Boddey
Oct 16, 2018·Chemical Biology & Drug Design·Kamila Anna MeissnerCarsten Wrenger
May 11, 2020·Cellular Microbiology·Anat FlorentinVasant Muralidharan
May 13, 2020·The New Phytologist·Petra C BoevinkStephen C Whisson
Mar 22, 2016·Molecular Microbiology·Jude M PrzyborskiMichael Lanzer
Jun 15, 2019·Life Science Alliance·Jose ThekkiniathChoukri Ben Mamoun
Sep 9, 2016·Genome Medicine·Sebastian KirchnerAndrew P Waters
Mar 7, 2020·Journal of Cell Science·Tolga O Bozkurt, Sophien Kamoun
May 1, 2021·Pathogens·Raghavendra YadavalliTobili Y Sam-Yellowe
Jan 9, 2020·Journal of Medicinal Chemistry·Peter Mubanga CheukaKelly Chibale

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Methods Mentioned

BETA
surface plasmon resonance
chip
gel filtration
isothermal titration calorimetry
immunoprecipitation
enzyme-linked immunosorbent assay
ELISA
transgenic
biosensors
PCR

Software Mentioned

Proteome
Prism
Quantity One
SoftWorx
Adobe Photoshop and Illustrator
Scaffold
MASCOT
ImageJ Fiji
Zeiss AxioVision
Corel PHOTO - PAINT X4

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