Subcellular localization of 14-3-3 proteins in<i>Toxoplasma gondii</i>tachyzoites and evidence for a lipid raft-associated form

Assossou, Olga; Besson, Françoise; Rouault, Jean‐Pierre; Persat, Florence; Brisson, Christine; Duret, Laurent; Ferrandiz, Josette; Mayençon, Martine; Peyron, François; Picot, Stéphane

doi:10.1016/s0378-1097(03)00479-8

Cited by 35 publications

(33 citation statements)

References 38 publications

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“…The localization of 14-3-3 proteins in different subcellular compartments and in association with membrane proteins has been widely demonstrated (37,38), and a lipid raft-associated form of the T. gondii 14-3-3 homolog has been recently described (13).…”

Section: Discussionmentioning

confidence: 99%

“…Preliminary studies, which have mainly focused on expression and localization, have been conducted on Plasmodium falciparum, Plasmodium knowlesi, Toxoplasma gondii, and Eimeria tenella, and the results have suggested that 14-3-3s play a role in the transmission of the regulatory signals involved in a wide array of biological processes, including the proliferation and migration of the parasite during infection (2,12,13).…”

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confidence: 99%

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The Giardia duodenalis 14-3-3 Protein Is Post-translationally Modified by Phosphorylation and Polyglycylation of the C-terminal Tail

Lalle

Salzano

Crescenzi

et al. 2006

Journal of Biological Chemistry

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The flagellated protozoan Giardia duodenalis (syn. lamblia or intestinalis) has been chosen as a model parasite to further investigate the multifunctional 14-3-3s, a family of highly conserved eukaryotic proteins involved in many cellular processes, such as cell cycle, differentiation, apoptosis, and signal transduction pathways. We confirmed the presence of a single 14-3-3 homolog gene (g14-3-3) by an in silico screening of the complete genome of Giardia, and we demonstrated its constitutive transcription throughout the life stages of the parasite. We cloned and expressed the g14-3-3 in bacteria, and by protein-protein interaction assays we demonstrated that it is a functional 14-3-3. Using an anti-peptide antibody raised against a unique 18-amino acid sequence at the N terminus, we observed variations both in the intracellular localization and in the molecular size of the native g14-3-3 during the conversion of Giardia from trophozoites to the cyst stage. An affinity chromatography, based on the 14-3-3 binding to the polypeptide difopein, was set to purify the native g14-3-3. By matrix-assisted laser desorption ionization mass spectroscopy analysis, we showed that polyglycylation, an unusual post-translational modification described only for tubulin, occurred at the extreme C terminus of the native g14-3-3 on Glu 246 , Glu 247 , or both and that the Thr 214 , located in the loop between helices 8 and 9, is phosphorylated. We propose that the addition of the polyglycine chain can promote the binding of g14-3-3 to alternative ligands and that the differential rate of polyglycylation/deglycylation during the encystation process can act as a novel mechanism to regulate the intracellular localization of g14-3-3.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Giardia duodenalis 14-3-3 Protein Is Post-translationally Modified by Phosphorylation and Polyglycylation of the C-terminal Tail

Lalle

Salzano

Crescenzi

et al. 2006

Journal of Biological Chemistry

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“…72 14-3-3 proteins have been detected in the asexual form of the parasite, namely the tachyzoite stage, that is virulent in humans. 73 Moreover, it was demonstrated that, in this stage, 14-3-3 proteins from T. gondii induce hypermotility in infected host cells. 74 Alveolar echinococcosis (AE) is a rare parasitic disorder that occurs after ingestion of eggs of Echinococcus multilocularis.…”

Section: Intentionally Targetingmentioning

confidence: 98%

Modulators of Protein–Protein Interactions

et al. 2014

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Direct interactions between proteins are essential for the regulation of their functions in biological pathways. Targeting the complex network of protein−protein interactions (PPIs) has now been widely recognized as an attractive means to therapeutically intervene in disease states. Even though this is a challenging endeavor and PPIs have long been regarded as "undruggable" targets, the last two decades have seen an increasing number of successful examples of PPI modulators, resulting in growing interest in this field. PPI modulation requires novel approaches and the integrated efforts of multiple disciplines to be a fruitful strategy. This perspective focuses on the hub-protein 14-3-3, which has several hundred identified protein interaction partners, and is therefore involved in a wide range of cellular processes and diseases. Here, we aim to provide an integrated overview of the approaches explored for the modulation of 14-3-3 PPIs and review the examples resulting from these efforts in both inhibiting and stabilizing specific 14-3-3 protein complexes by small molecules, peptide mimetics, and natural products.

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“…For example, the single 14-3-3 protein in Giardia duodenalis has been found to be modified post-translationally in vivo and involved in a number of cellular processes [10]. The genome of Toxoplasma gondii , another Apicomplexa n parasite, encodes four putative 14-3-3 proteins, at least one of which may be membrane associated and an excreted/secreted antigen, suggesting its possible role as a vaccine candidate [11].…”

Section: Introductionmentioning

confidence: 99%

Characterization of 14-3-3 Proteins from Cryptosporidium parvum

et al. 2011

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The parasite Cryptosporidium parvum has three 14-3-3 proteins: Cp14ε, Cp14a and Cp14b, with only Cp14ε similar to human 14-3-3 proteins in sequence, peptide-binding properties and structure. Structurally, Cp14a features the classical 14-3-3 dimer but with a uniquely wide pocket and a disoriented RRY triad potentially incapable of binding phosphopeptides. The Cp14b protein deviates from the norm significantly: (i) In one subunit, the phosphorylated C-terminal tail is bound in the binding groove like a phosphopeptide. This supports our binding study indicating this protein was stabilized by a peptide mimicking its last six residues. (ii) The other subunit has eight helices instead of nine, with αA and αB forming a single helix and occluding the peptide-binding cleft. (iii) The protein forms a degenerate dimer with the two binding grooves divided and facing opposite directions. These features conspire to block and disrupt the bicameral substrate-binding pocket, suggesting a possible tripartite auto-regulation mechanism that has not been observed previously.Enhanced version This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

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Subcellular localization of 14-3-3 proteins inToxoplasma gondiitachyzoites and evidence for a lipid raft-associated form

Cited by 35 publications

References 38 publications

The Giardia duodenalis 14-3-3 Protein Is Post-translationally Modified by Phosphorylation and Polyglycylation of the C-terminal Tail

The Giardia duodenalis 14-3-3 Protein Is Post-translationally Modified by Phosphorylation and Polyglycylation of the C-terminal Tail

Modulators of Protein–Protein Interactions

Characterization of 14-3-3 Proteins from Cryptosporidium parvum

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