Protein Export Mechanisms in Malaria Parasites

Malaria parasites remodel their host erythrocytes and hepatocytes by exporting hundreds of effector proteins across multiple membrane barriers. Central to this process is the Plasmodium translocon of exported proteins (PTEX), a multi‐subunit channel in the parasitophorous vacuole membrane (PVM) that mediates the translocation of unfolded cargo. Proteins destined for export typically bear a pentapeptide signal known as the PEXEL motif, which is cleaved in the parasite endoplasmic reticulum by the protease Plasmepsin V. Unfolding is facilitated by chaperone components such as HSP101 before passage through PTEX, after which effectors refold and localise to specialised structures in the host cell. In red blood cells, exported proteins traffic via Maurer’s clefts before installation at knobs on the cell surface, enabling cytoadherence and immune evasion. During liver‐stage infection, analogous export pathways assemble at the hepatocyte‐derived PVM, underscoring a conserved requirement for protein delivery in different tissues. This coordinated export network underpins nutrient acquisition, virulence, host‐cell remodelling and stage‐specific development in malaria parasites, making each step a potential target for therapeutic intervention.

Research from Nature Portfolio

Enhanced proximity‐labelling approaches have been applied to decipher the interactome of exported virulence factors at the host–parasite interface. Using an engineered peroxidase tag fused to a key erythrocyte remodelling protein, researchers identified dozens of candidate partners within Maurer’s clefts and knob structures. This study illuminates the spatial assembly of export machinery and reveals novel components that may stabilise the architecture of exported organelles. These findings refine our understanding of how exported effectors are organised post‐translocation and suggest new targets for disrupting host‐cell remodelling.

Protein Export Mechanisms in Malaria Parasites publication trend

The graph below shows the total number of articles in protein export mechanisms in malaria parasites across all publications each year (not limited to Nature Index journals).

Technical terms

PEXEL motif: A pentapeptide sequence directing proteins for export through the parasite secretory pathway.

Plasmodium translocon of exported proteins (PTEX): A multiprotein complex that translocates unfolded parasite proteins across the PVM into the host cell.

Parasitophorous vacuole membrane (PVM): The membrane enclosing the parasite within the host cell.

Maurer’s clefts: Membranous compartments in infected erythrocytes that sort and traffic exported proteins.

Cytoadherence: The process by which infected erythrocytes adhere to vascular endothelium, mediated by exported proteins assembled in knob structures.

References

1. Flp/FRT-mediated disruption of ptex150 and exp2 in Plasmodium falciparum sporozoites inhibits liver-stage development. Proceedings of the National Academy of Sciences of the United States of America (2024).
2. PTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum. PLOS Pathogens (2023).
3. APEX2-based proximity proteomic analysis identifies candidate interactors for Plasmodium falciparum knob-associated histidine-rich protein in infected erythrocytes. Scientific Reports (2024).
4. Time-resolved proximity biotinylation implicates a porin protein in export of transmembrane malaria parasite effectors. Journal of Cell Science (2023).