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Open Access Research

Interaction of an atypical Plasmodium falciparum ETRAMP with human apolipoproteins

Marissa Vignali1, Anastasia McKinlay12, Douglas J LaCount12, Rakesh Chettier3, Russell Bell3, Sudhir Sahasrabudhe3, Robert E Hughes3 and Stanley Fields12*

Author Affiliations

1 Departments of Genome Sciences and Medicine, University of Washington, Box 355065, Seattle, WA 98195, USA

2 Howard Hughes Medical Institute, USA

3 Prolexys Pharmaceuticals, Inc., 2150 West Dauntless Avenue, Salt Lake City, Utah 84116, USA

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Malaria Journal 2008, 7:211  doi:10.1186/1475-2875-7-211

Published: 20 October 2008

Abstract

Background

In order to establish a successful infection in the human host, the malaria parasite Plasmodium falciparum must establish interactions with a variety of human proteins on the surface of different cell types, as well as with proteins inside the host cells. To better understand this aspect of malaria pathogenesis, a study was conducted with the goal of identifying interactions between proteins of the parasite and those of its human host.

Methods

A modified yeast two-hybrid methodology that preferentially selects protein fragments that can be expressed in yeast was used to conduct high-throughput screens with P. falciparum protein fragments against human liver and cerebellum libraries. The resulting dataset was analyzed to exclude interactions that are not likely to occur in the human host during infection.

Results

An initial set of 2,200 interactions was curated to remove proteins that are unlikely to play a role in pathogenesis based on their annotation or localization, and proteins that behave promiscuously in the two-hybrid assay, resulting in a final dataset of 456 interactions. A cluster that implicates binding between P. falciparum PFE1590w/ETRAMP5, a putative parasitophorous vacuole membrane protein, and human apolipoproteins ApoA, ApoB and ApoE was selected for further analysis. Different isoforms of ApoE, which are associated with different outcomes of malaria infection, were shown to display differential interactions with PFE1590w.

Conclusion

A dataset of interactions between proteins of P. falciparum and those of its human host was generated. The preferential interaction of the P. falciparum PFE1590w protein with the human ApoE ε3 and ApoE ε4 isoforms, but not the ApoE ε2 isoform, supports the hypothesis that ApoE genotype affects risk of malaria infection. The dataset contains other interactions of potential relevance to disease that may identify possible vaccine candidates and drug targets.