Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1

0463304 - BC 2017 RIV CH eng J - Článek v odborném periodiku
Tellier, G. - Lenne, A. - Cailliau-Maggio, K. - Cabezas-Cruz, A. - Valdés, James J. - Martoriati, A. - Aliouat, El M. - Gosset, P. - Delaire, B. - Fréville, A. - Pierrot, C. - Khalife, J.
Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1.
Frontiers in Microbiology. Roč. 7, MAY 26 (2016), č. článku 777. ISSN 1664-302X. E-ISSN 1664-302X
Institucionální podpora: RVO:60077344
Klíčová slova: Plasmodium falciparum * Protein Phosphatase type1 * eIF2b * protein-protein interaction * translation complex
Kód oboru RIV: EE - Mikrobiologie, virologie
Impakt faktor: 4.076, rok: 2016

Protein phosphatase 1 (PP1c) is one of the main phosphatases whose function is shaped by many regulators to confer a specific location and a selective function for this enzyme. Here, we report that eukaryotic initiation factor 2 beta of Plasmodium falciparum (PfelF2 beta) is an interactor of PfPP1c. Sequence analysis of PfelF2 beta revealed a deletion of 111 amino acids when compared to its human counterpart and the presence of two potential binding motifs to PfPP1 ((29)FGEKKK(34), (103)KVAW(106)). As expected, we showed that PfelF2 beta binds PfelF2 gamma and PfelF5, confirming its canonical interaction with partners of the translation complex. Studies of the PfelF2 beta-PfPP1 interaction using wild-type, single and double mutated versions of PfelF2 beta revealed that both binding motifs are critical. We next showed that PfelF2 beta is able to induce Germinal Vesicle Break Down (GVBD) when expressed in Xenopus oocytes, an indicator of its capacity to regulate PP1. Only combined mutations of both binding motifs abolished the interaction with PP1 and the induction of GVBD. In P falciparum, although the locus is accessible for genetic manipulation, PfelF2 beta seems to play an essential role in intraerythrocytic cycle as no viable knockout parasites were detectable. Interestingly, as for PfPP1, the subcellular fractionation of P falciparum localized PfelF2 beta in cytoplasm and nuclear extracts, suggesting a potential effect on PfPP1 in both compartments and raising the question of a non-canonical function of Pfelf2 beta in the nucleus. Hence, the role played by PfelF2 beta in blood stage parasites could occur at multiple levels involving the binding to proteins of the translational complex and to PfPP1.
Trvalý link: http://hdl.handle.net/11104/0262530