Regions of Intrinsic Disorder Help Identify a Novel Nuclear Localization Signal in toxoplasma Gondii Histone Acetyltransferase Tggcn5-b

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Apicomplexa, Parasite, Cellular Trafficking, GCN5, Chromatin, Epigenetics

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We have previously shown that protozoan parasites, such as Toxoplasma gondii, contain a high prevalence of intrinsically disordered regions in their predicted proteins. Here, we determine that both TgGCN5-family histone acetyltransferases (HATs) contain unusually high levels of intrinsic disorder. A previously identified basic-rich nuclear localization signal (NLS) in the N-terminus of TgGCN5-A is located within such a region of predicted disorder, but this NLS is not conserved in TgGCN5-B. We therefore analyzed the intrinsically disordered regions of TgGCN5-B for basic-rich sequences that could be indicative of a functional NLS, and this led to the identification of a novel NLS for TgGCN5-B, RPAENKKRGR. The functionality of the GCN5-B NLS was validated experimentally and has predictive value. These studies demonstrate that basic-rich sequences within regions predicted to be intrinsically disordered constitute criteria for a candidate NLS.

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Citation / Publisher Attribution

Molecular and Biochemical Parasitology, v. 175, issue 2, p. 192-195