Authors

Discussion

Protein-protein interactions are essential in broad range of biological processes including the post-translational modifications. Substrate-kinase or phosphatase interactions are considered as transient binding and play a central and essential role in Plasmodium cell cycle. The Ser/Thr Protein Phosphatase Type 1 (PP1) is essential to cell viability in P. falciparum and is regulated by the binding of regulatory subunits, up to 200 in humans, but only 4 have been reported for the parasite.

To explore the P. falciparum PP1 (PfPP1) regulatory network, we carry out three strategies to characterize its interactome. Co-affinity purification followed by MS analysis identified 6 PfPP1 interacting proteins of which 3 contained the RVxF consensus binding, 2 with a Fxx[RK]x[RK] motif, also shown to be interact with PP1 and one with both binding motifs. The Yeast Two-Hybrid screens identified 134 proteins of which 30 present the RVxF motif and 20 have the Fxx[RK]x[RK] motif. The in silico screen using a consensus RVxF motif as template revealed the presence of 55 potential PfPP1 interacting proteins. As further demonstration, 35 candidate partners were validated in an ELISA-based assay. The data reports several conserved PP1 interacting proteins as well as a high number of specific interactors to PfPP1 and indicates a high diversity of biological functions for PP1 in Plasmodium. Among these candidates, the Gametocyte EXported Protein 15 has been confirmed as true interactor of PfPP1 by different approaches. GEXP15 is over-expressed during gametocyte stage, responsible for the transmission of the parasite in the mosquito. These results as well as functional studies will be presented.