In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 2 ( 2022-2-22), p. e1009977-
Abstract:
Plasmodium falciparum exports ~10% of its proteome into its host erythrocyte to modify the host cell’s physiology. The Plasmodium export element (PEXEL) motif contained within the N-terminus of most exported proteins directs the trafficking of those proteins into the erythrocyte. To reach the host cell, the PEXEL motif of exported proteins is processed by the endoplasmic reticulum (ER) resident aspartyl protease plasmepsin V. Then, following secretion into the parasite-encasing parasitophorous vacuole, the mature exported protein must be unfolded and translocated across the parasitophorous vacuole membrane by the Plasmodium translocon of exported proteins (PTEX). PTEX is a protein-conducting channel consisting of the pore-forming protein EXP2, the protein unfoldase HSP101, and structural component PTEX150. The mechanism of how exported proteins are specifically trafficked from the parasite’s ER following PEXEL cleavage to PTEX complexes on the parasitophorous vacuole membrane is currently not understood. Here, we present evidence that EXP2 and PTEX150 form a stable subcomplex that facilitates HSP101 docking. We also demonstrate that HSP101 localises both within the parasitophorous vacuole and within the parasite’s ER throughout the ring and trophozoite stage of the parasite, coinciding with the timeframe of protein export. Interestingly, we found that HSP101 can form specific interactions with model PEXEL proteins in the parasite’s ER, irrespective of their PEXEL processing status. Collectively, our data suggest that HSP101 recognises and chaperones PEXEL proteins from the ER to the parasitophorous vacuole and given HSP101’s specificity for the EXP2-PTEX150 subcomplex, this provides a mechanism for how exported proteins are specifically targeted to PTEX for translocation into the erythrocyte.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009977
DOI:
10.1371/journal.ppat.1009977.g001
DOI:
10.1371/journal.ppat.1009977.g002
DOI:
10.1371/journal.ppat.1009977.g003
DOI:
10.1371/journal.ppat.1009977.g004
DOI:
10.1371/journal.ppat.1009977.g005
DOI:
10.1371/journal.ppat.1009977.g006
DOI:
10.1371/journal.ppat.1009977.g007
DOI:
10.1371/journal.ppat.1009977.g008
DOI:
10.1371/journal.ppat.1009977.s001
DOI:
10.1371/journal.ppat.1009977.s002
DOI:
10.1371/journal.ppat.1009977.s003
DOI:
10.1371/journal.ppat.1009977.s004
DOI:
10.1371/journal.ppat.1009977.s005
DOI:
10.1371/journal.ppat.1009977.s006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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