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Issue 4, 2013
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Protein intrinsic disorder in the acetylome of intracellular and extracellular Toxoplasma gondii

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Abstract

Toxoplasma gondii is an obligate intracellular parasite of the phylum Apicomplexa, which includes a number of species of medical and veterinary importance. Inhibitors of lysine deacetylases (KDACs) exhibit potent antiparasitic activity, suggesting that interference with lysine acetylation pathways holds promise for future drug targeting. Using high resolution LC-MS/MS to identify parasite peptides enriched by immunopurification with acetyl-lysine antibody, we recently produced an acetylome of the proliferative intracellular stage of Toxoplasma. In this study, we used similar approaches to greatly expand the Toxoplasma acetylome by identifying acetylated proteins in non-replicating extracellular tachyzoites. The functional breakdown of acetylated proteins in extracellular parasites is similar to intracellular parasites, with an enrichment of proteins involved in metabolism, translation, and chromatin biology. Altogether, we have now detected over 700 acetylation sites on a wide variety of parasite proteins of diverse function in multiple subcellular compartments. We found 96 proteins uniquely acetylated in intracellular parasites, 216 uniquely acetylated in extracellular parasites, and 177 proteins acetylated in both states. Our findings suggest that dramatic changes occur at the proteomic level as tachyzoites transition from the intracellular to the extracellular environment, similar to reports documenting significant changes in gene expression during this transition. The expanded dataset also allowed a thorough analysis of the degree of protein intrinsic disorder surrounding lysine residues targeted for this post-translational modification. These analyses indicate that acetylated lysines in proteins from extracellular and intracellular tachyzoites are largely located within similar local environments, and that lysine acetylation preferentially occurs in intrinsically disordered or flexible regions.

Graphical abstract: Protein intrinsic disorder in the acetylome of intracellular and extracellular Toxoplasma gondii

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Publication details

The article was received on 12 Nov 2012, accepted on 22 Jan 2013 and first published on 22 Jan 2013


Article type: Paper
DOI: 10.1039/C3MB25517D
Citation: Mol. BioSyst., 2013,9, 645-657
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    Protein intrinsic disorder in the acetylome of intracellular and extracellular Toxoplasma gondii

    B. Xue, V. Jeffers, W. J. Sullivan and V. N. Uversky, Mol. BioSyst., 2013, 9, 645
    DOI: 10.1039/C3MB25517D

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