van Ooij, Christiaan;
Withers-Martinez, Chrislaine;
Ringel, Alessa;
Cockcroft, Shamshad;
Haldar, Kasturi;
Blackman, Michael J;
(2013)
Identification of a Plasmodium falciparum Phospholipid Transfer Protein.
Journal of Biological Chemistry (JBC)
, 288
(44)
pp. 31971-31983.
10.1074/jbc.M113.474189.
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Abstract
Infection of erythrocytes by the human malaria parasite Plasmodium falciparum results in dramatic modifications to the host cell, including changes to its antigenic and transport properties and the de novo formation of membranous compartments within the erythrocyte cytosol. These parasite-induced structures are implicated in the transport of nutrients, metabolic products, and parasite proteins, as well as in parasite virulence. However, very few of the parasite effector proteins that underlie remodeling of the host erythrocyte are functionally characterized. Using bioinformatic examination and modeling, we have found that the exported P. falciparum protein PFA0210c belongs to the START domain family, members of which mediate transfer of phospholipids, ceramide, or fatty acids between membranes. In vitro phospholipid transfer assays using recombinant PFA0210 confirmed that it can transfer phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin between phospholipid vesicles. Furthermore, assays using HL60 cells containing radiolabeled phospholipids indicated that orthologs of PFA0210c can also transfer phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. Biochemical and immunochemical analysis showed that PFA0210c associates with membranes in infected erythrocytes at mature stages of intracellular parasite growth. Localization studies in live parasites revealed that the protein is present in the parasitophorous vacuole during growth and is later recruited to organelles in the parasite. Together these data suggest that PFA0210c plays a role in the formation of the membranous structures and nutrient phospholipid transfer in the malaria-parasitized erythrocyte.// Background: PFA0210c is an exported Plasmodium falciparum protein.// Results: PFA0210c is a phospholipid transfer protein with similarities to proteins of the family of START domain-containing proteins and can transfer various phospholipids between membranes in vitro.// Conclusion: PFA0210c and its orthologs are phospholipid transfer proteins with a broad specificity.// Significance: Identification of the function of conserved Plasmodium proteins allows deeper insight into the basis of pathogenesis.
| Type: | Article |
|---|---|
| Title: | Identification of a Plasmodium falciparum Phospholipid Transfer Protein |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1074/jbc.M113.474189 |
| Publisher version: | https://doi.org/10.1074/jbc.M113.474189 |
| Language: | English |
| Additional information: | © The Author(s), 2021. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Lipid Transport, Malaria, Parasitology, Phospholipid, Plasmodium, Phospholipid Transfer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10177178 |
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