Identification of Toxoplasma TgPH1, a pleckstrin homology domain-containing protein that binds to the phosphoinositide PI(3,5)P2

Mol Biochem Parasitol. 2016 May;207(1):39-44. doi: 10.1016/j.molbiopara.2016.03.011. Epub 2016 Apr 7.

Abstract

The phosphoinositide phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2) plays crucial roles in the maintenance of lysosome/vacuole morphology, membrane trafficking and regulation of endolysosome-localized membrane channel activity. In Toxoplasma gondii, we previously reported that PI(3,5)P2 is essential for parasite survival by controlling homeostasis of the apicoplast, a particular organelle of algal origin. Here, by using a phosphoinositide pull-down assay, we identified TgPH1 in Toxoplasma a protein conserved in many apicomplexan parasites. TgPH1 binds specifically to PI(3,5)P2, shows punctate intracellular localization, but plays no vital role for tachyzoite growth in vitro. TgPH1 is a protein predominantly formed by a pleckstrin homology (PH) domain. So far, PH domains have been described to bind preferentially to bis- or trisphosphate phosphoinositides containing two adjacent phosphates (i.e. PI(3,4)P2, PI(4,5)P2, PI(3,4,5)P3). Therefore, our study reveals an unusual feature of TgPH1 which binds preferentially to PI(3,5)P2.

Keywords: Apicoplast; PI(3,5)P(2); Phosphoinositides; Pleckstrin Homology domain; Toxoplasma gondii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Gene Deletion
  • Gene Expression
  • Phosphatidylinositol Phosphates / metabolism*
  • Pleckstrin Homology Domains* / genetics
  • Protein Binding
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Toxoplasma / genetics
  • Toxoplasma / metabolism*

Substances

  • Phosphatidylinositol Phosphates
  • Protozoan Proteins
  • phosphatidylinositol 3,5-diphosphate