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Tellier G, Lenne A, Cailliau-Maggio K, et al. Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1. Front Microbiol. 2016;7:777doi: 10.3389/fmicb.2016.00777.
Tellier, G., Lenne, A., Cailliau-Maggio, K., Cabezas-Cruz, A., Valdés, J. J., Martoriati, A., Aliouat, e. l. . M., Gosset, P., Delaire, B., Fréville, A., Pierrot, C., & Khalife, J. (2016). Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1. Frontiers in microbiology, 7777. https://doi.org/10.3389/fmicb.2016.00777
Tellier, Géraldine, et al. "Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1." Frontiers in microbiology vol. 7 (2016): 777. doi: https://doi.org/10.3389/fmicb.2016.00777
Tellier G, Lenne A, Cailliau-Maggio K, Cabezas-Cruz A, Valdés JJ, 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. Front Microbiol. 2016 May 26;7:777. doi: 10.3389/fmicb.2016.00777. eCollection 2016. PMID: 27303372; PMCID: PMC4881399.
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Front Microbiol. 2016 May 26;7:777. doi: 10.3389/fmicb.2016.00777. eCollection 2016.

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

Frontiers in microbiology

Géraldine Tellier, Astrid Lenne, Katia Cailliau-Maggio, Alejandro Cabezas-Cruz, James J Valdés, Alain Martoriati, El M Aliouat, Pierre Gosset, Baptiste Delaire, Aline Fréville, Christine Pierrot, Jamal Khalife

Affiliations

  1. Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Centre d'Infection et d'Immunité de Lille, Université de Lille Lille, France.
  2. Centre National de la Recherche Scientifique, UMR 8576 - Unité de Glycobiologie Structurale et Fonctionnelle, Université de Lille Lille, France.
  3. Institute of Parasitology, The Czech Academy of Sciences?eské Bud?jovice, Czech Republic; Department of Virology, Veterinary Research InstituteBrno, Czech Republic.
  4. Service d'Anatomie et de Cytologie Pathologiques, Groupe Hospitalier de l'Université Catholique de Lille Lille, France.

PMID: 27303372 PMCID: PMC4881399 DOI: 10.3389/fmicb.2016.00777

Abstract

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 2β of Plasmodium falciparum (PfeIF2β) is an interactor of PfPP1c. Sequence analysis of PfeIF2β 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 PfeIF2β binds PfeIF2γ and PfeIF5, confirming its canonical interaction with partners of the translation complex. Studies of the PfeIF2β-PfPP1 interaction using wild-type, single and double mutated versions of PfeIF2β revealed that both binding motifs are critical. We next showed that PfeIF2β 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, PfeIF2β 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 PfeIF2β in cytoplasm and nuclear extracts, suggesting a potential effect on PfPP1 in both compartments and raising the question of a non-canonical function of PfeIf2β in the nucleus. Hence, the role played by PfeIF2β in blood stage parasites could occur at multiple levels involving the binding to proteins of the translational complex and to PfPP1.

Keywords: Plasmodium falciparum; Protein Phosphatase type 1; eIF2β; protein-protein interaction; translation complex

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