ArticlePLoS biology2014
Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites.
Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 162 citations in OpenAlex.
- Plasmepsins as Antimalarial Drug Targets-Then, Now, and the Future.Medicinal research reviews · 2026Review
- Identification of a Novel 1,3,4-Thiadiazole-Based Scaffold as a Plasmepsin V Inhibitor.ACS omega · 2026Article
- The inner membrane complex protein, IMC55, is dispensable for intraerythrocytic development ofMicrobiology spectrum · 2026Article
- Identification of a Putative Metal Transporter in the Apicoplast of Malaria Parasites.bioRxiv : the preprint server for biology · 2026Article
- Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum.Malaria journal · 2026Article
- Deconvolution of the On-Target Activity of Plasmepsin V Peptidomimetics inACS infectious diseases · 2025Article
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- An overview of the interconnectedness of the PEXEL and non-PEXEL mediated protein export iniScience · 2025Review
- Biotransformation of medicarpin from homopterocarpin by Aspergillus niger and its biological characterization.Scientific reports · 2025Article
- Structure-activity analysis of imino-pyrimidinone-fused pyrrolidines aids the development of dual plasmepsin V and plasmepsin X inhibitors.The FEBS journal · 2025Article
- Reversible host cell surface remodelling limits immune recognition and maximizes survival of Plasmodium falciparum gametocytes.PLoS pathogens · 2025Article
- The threemSphere · 2024Article
- Flp/Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.International journal of molecular sciences · 2024Review
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- Sequence elements within the PEXEL motif and its downstream region modulate PTEX-dependent protein export in Plasmodium falciparum.Traffic (Copenhagen, Denmark) · 2024Article
- The mature N-termini ofmBio · 2023Article
- Knock-sideways by inducible ER retrieval enables a unique approach for studyingProceedings of the National Academy of Sciences of the United States of America · 2023Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The malaria parasite Plasmodium falciparum exports several hundred proteins into the infected erythrocyte that are involved in cellular remodeling and severe virulence. The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease, Plasmepsin V (PMV). The PMV gene is refractory to deletion, suggesting it is essential, but definitive proof is lacking. Here, we generated a PEXEL-mimetic inhibitor that potently blocks the activity of PMV isolated from P. falciparum and Plasmodium vivax. Assessment of PMV activity in P. falciparum revealed PEXEL cleavage occurs cotranslationaly, similar to signal peptidase. Treatment of P. falciparum-infected erythrocytes with the inhibitor caused dose-dependent inhibition of PEXEL processing as well as protein export, including impaired display of the major virulence adhesin, PfEMP1, on the erythrocyte surface, and cytoadherence. The inhibitor killed parasites at the trophozoite stage and knockdown of PMV enhanced sensitivity to the inhibitor, while overexpression of PMV increased resistance. This provides the first direct evidence that PMV activity is essential for protein export in Plasmodium spp. and for parasite survival in human erythrocytes and validates PMV as an antimalarial drug target.
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