Regions of intrinsic disorder help identify a novel nuclear localization signal in Toxoplasma gondii histone acetyltransferase TgGCN5-B.
Regions of intrinsic disorder help identify a novel nuclear localization signal in Toxoplasma gondii histone acetyltransferase TgGCN5-B.
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DOI：
10.1016/j.molbiopara.2010.10.009
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发表时间：
2011-02
影响因子：
1.5
通讯作者：
Sullivan, William J., Jr.
中科院分区：
文献类型：
--
作者：
Dixon, Stacy E.;Bhatti, Micah M.;Uversky, Vladimir N.;Dunker, A. Keith;Sullivan, William J., Jr.
我们以前已经表明，原生动物寄生虫，如弓形虫，包含一个高患病率的内在无序区域在其预测的蛋白质。在这里，我们确定这两个TgGCN 5家族的组蛋白乙酰转移酶（HAT）含有异常高水平的内在障碍。先前在TgGCN 5-A的N-末端中鉴定的富含碱性的核定位信号（NLS）位于预测的病症的这种区域内，但是该NLS在TgGCN 5-B中不保守。因此，我们分析了TgGCN 5-B的固有无序区域，以寻找可能指示功能性NLS的富含碱性的序列，并且这导致鉴定了TgGCN 5-B的新型NLS，RPAENKKRGR。实验验证了GCN 5-B NLS的功能，并具有预测价值。这些研究表明，预测为内在无序的区域内的富含碱性的序列构成候选NLS的标准。
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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