Identification of a Plasmodium falciparum Phospholipid Transfer Protein

Abstract

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.

Critical Steps in Protein Export of Plasmodium falciparum Blood Stages

“…The next important goal is the functional characterisation of these proteins (see Outstanding Questions Box), which has so far predominantly yielded data on functions in host cell rigidity and PfEMP1 transport and display [77,78,[95][96][97][98][99]. There are likely to be many other functions of exported proteins that have so far remained obscure, such as the recently discovered functions in intercellular communication [90,91] and lipid biology [100], or for which the molecular basis was previously unknown, such as in the rosetting of infected red blood cells [101].…”

Regulation and Essentiality of the StAR-related Lipid Transfer (START) Domain-containing Phospholipid Transfer Protein PFA0210c in Malaria Parasites

“…We subsequently showed that PFA0210c as well as its orthologues in the simian and human malaria pathogen P. knowlesi (PKH_020910 or PKNH_0209300) and the rodent parasite Plasmodium chabaudi (PCHAS_020730 or PCHAS_0207300) are phospholipid transfer proteins that can transfer a broad range of phospholipids in vitro (24). All three proteins contain a signal sequence and a predicted PEXEL motif that directs export from the parasite into the host erythrocyte (Fig.…”

“…is the exported broad specificity phospholipid transfer protein PFA0210c (PF3D7_0104200). PSI-BLAST analysis shows that PFA0210c is most closely related to STARD7, whereas structure prediction reveals that the highest similarity is to human phosphatidylcholine transfer protein STARD2 (24). …”

“…How the parasite transfers phospholipids across the aqueous environment of the parasitophorous vacuole lumen to the parasitophorous membrane and the Maurer's clefts is unknown. It has been suggested that PFA0210c may play a part in this process (24). In support of this, a unique feature of PFA0210c among the Plasmodium falciparum START proteins is the presence of a signal sequence, which mediates the secretion of the protein from the parasite into the parasitophorous vacuole, as well as a PEXEL export signal, which directs export beyond the parasitophorous vacuole membrane into the erythrocyte cytosol (Fig.…”

“…1 A ). Previous studies have indicated that PFA0210c can be exported from the parasite to the erythrocyte cytosol (29), although at least a fraction remains in the parasitophorous vacuole (24). The presence of the protein at these locations indicates that it may function to transfer phospholipids between the parasite and parts of the exomembrane system.…”