Several hundred malaria parasite proteins are exported beyond an encasing vacuole and into the cytosol of the host erythrocyte, a process that is central to the virulence and viability of the causative Plasmodium species. The trafficking machinery responsible for this export is unknown. Here we identify in Plasmodium falciparum a translocon of exported proteins (PTEX), which is located in the vacuole membrane. The PTEX complex is ATP-powered, and comprises heat shock protein 101 (HSP101; a ClpA/B-like ATPase from the AAA+ superfamily, of a type commonly associated with protein translocons), a novel protein termed PTEX150 and a known parasite protein, exported protein 2 (EXP2). EXP2 is the potential channel, as it is the membrane-associated component of the core PTEX complex. Two other proteins, a new protein PTEX88 and thioredoxin 2 (TRX2), were also identified as PTEX components. As a common portal for numerous crucial processes, this translocon offers a new avenue for therapeutic intervention.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725363 | PMC |
| http://dx.doi.org/10.1038/nature08104 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Flp/-mediated disruption of and in sporozoites inhibits liver-stage development.
Proc Natl Acad Sci U S A
July 2024
Division of Infectious Diseases & Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
causes severe malaria and assembles a protein translocon (PTEX) complex at the parasitophorous vacuole membrane (PVM) of infected erythrocytes, through which several hundred proteins are exported to facilitate growth. The preceding liver stage of infection involves growth in a hepatocyte-derived PVM; however, the importance of protein export during liver infection remains unexplored. Here, we use the FlpL/ system to conditionally excise genes in sporozoites for functional liver-stage studies.
View Article and Find Full Text PDFSequence elements within the PEXEL motif and its downstream region modulate PTEX-dependent protein export in Plasmodium falciparum.
Traffic
January 2024
Malaria Virulence and Drug Discovery Group, Burnet Institute, Melbourne, Victoria, Australia.
Article Synopsis
- - The parasite Plasmodium falciparum, responsible for severe malaria, invades red blood cells by exporting hundreds of proteins that modify the host cell to enhance parasite growth and evade the immune system.
- - These exported proteins contain a specific motif (PEXEL) that signals their processing and export, involving a proteolytic cleavage step in the parasite’s endoplasmic reticulum, which assists in the release of proteins into the host cell's vacuole.
- - The study reveals that the PEXEL's sequence and a 'spacer' region between the PEXEL and functional protein regions are crucial for the protein's recognition and efficient transport by the PTEX complex into the red blood cells.
Knock-sideways by inducible ER retrieval enables a unique approach for studying secreted proteins.
Proc Natl Acad Sci U S A
August 2023
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011.
Malaria parasites uniquely depend on protein secretion for their obligate intracellular lifestyle but approaches for dissecting -secreted protein functions are limited. We report knockER, a unique DiCre-mediated knock-sideways approach to sequester secreted proteins in the ER by inducible fusion with a KDEL ER-retrieval sequence. We show conditional ER sequestration of diverse proteins is not generally toxic, enabling loss-of-function studies.
View Article and Find Full Text PDFPTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum.
PLoS Pathog
July 2023
Malaria Virulence and Drug Discovery Group, Burnet Institute, Melbourne, Australia.
A key element of Plasmodium biology and pathogenesis is the trafficking of ~10% of the parasite proteome into the host red blood cell (RBC) it infects. To cross the parasite-encasing parasitophorous vacuole membrane, exported proteins utilise a channel-forming protein complex termed the Plasmodium translocon of exported proteins (PTEX). PTEX is obligatory for parasite survival, both in vitro and in vivo, suggesting that at least some exported proteins have essential metabolic functions.
View Article and Find Full Text PDFHemoglobin degradation is crucial for the growth and survival of in human erythrocytes. Although the process of Hb degradation has been studied in detail, the mechanisms of Hb uptake remain ambiguous to date. Here, we characterized Heme Detoxification Protein (HDP); a protein localized in the parasitophorus vacuole, parasite food vacuole, and infected erythrocyte cytosol for its role in Hb uptake.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!