Interaction of an atypical Plasmodium falciparum ETRAMP with human apolipoproteins View Full Text


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Article Info

DATE

2008-10-20

AUTHORS

Marissa Vignali, Anastasia McKinlay, Douglas J LaCount, Rakesh Chettier, Russell Bell, Sudhir Sahasrabudhe, Robert E Hughes, Stanley Fields

ABSTRACT

BackgroundIn 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.MethodsA 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.ResultsAn 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.ConclusionA 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. More... »

PAGES

211

References to SciGraph publications

  • 2002-10. A proteomic view of the Plasmodium falciparum life cycle in NATURE
  • 2004-12-05. Genetically modified Plasmodium parasites as a protective experimental malaria vaccine in NATURE
  • 2008. GeneCards in ENCYCLOPEDIA OF GENETICS, GENOMICS, PROTEOMICS AND INFORMATICS
  • 2006-02-20. Lineage-specific expansion of proteins exported to erythrocytes in malaria parasites in GENOME BIOLOGY
  • 2007-04. How HIV-1 hijacks ALIX in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2008. GeneDB in ENCYCLOPEDIA OF GENETICS, GENOMICS, PROTEOMICS AND INFORMATICS
  • 2005-11. A protein interaction network of the malaria parasite Plasmodium falciparum in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1475-2875-7-211

    DOI

    http://dx.doi.org/10.1186/1475-2875-7-211

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1002596479

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18937849


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