Proteome-wide prediction of acetylation substrates
Proteome-wide prediction of acetylation substrates
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DOI：
10.1073/pnas.0906801106
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发表时间：
2009-08-18
影响因子：
11.1
通讯作者：
Hake, Sandra B.
中科院分区：
文献类型：
--
作者：
Basu, Amrita;Rose, Kristie L.;Hake, Sandra B.
乙酰化是一种广泛研究的翻译后修饰，与广泛的生物学过程，特别是基因调控有关。许多研究有助于我们了解乙酰化的酶学基础，包括了解几种乙酰转移酶底物识别的分子机制，但传统的实验来确定底物位点特异性的内在特征已被证明具有挑战性。在这里，我们结合联合收割机的实验方法与蛋白质序列的聚类分析，预测蛋白质乙酰化的基础上的乙酰化赖氨酸的序列特征与我们独特的预测工具PredMod。我们定义了一个本地的氨基酸序列组成，代表潜在的乙酰化位点，通过实施聚类分析的组蛋白和非组蛋白序列。我们表明，这种序列组合物具有预测能力的2个独立的实验数据集的乙酰化标记。最后，我们检测乙酰化选定的推定基板使用质谱，并报告几个非组蛋白乙酰化底物芽殖酵母。我们的方法与更传统的实验方法相结合，可能有助于识别整个蛋白质组的乙酰化底物。
Acetylation is a well-studied posttranslational modification that has been associated with a broad spectrum of biological processes, notably gene regulation. Many studies have contributed to our knowledge of the enzymology underlying acetylation, including efforts to understand the molecular mechanism of substrate recognition by several acetyltransferases, but traditional experiments to determine intrinsic features of substrate site specificity have proven challenging. Here, we combine experimental methods with clustering analysis of protein sequences to predict protein acetylation based on the sequence characteristics of acetylated lysines within histones with our unique prediction tool PredMod. We define a local amino acid sequence composition that represents potential acetylation sites by implementing a clustering analysis of histone and nonhistone sequences. We show that this sequence composition has predictive power on 2 independent experimental datasets of acetylation marks. Finally, we detect acetylation for selected putative substrates using mass spectrometry, and report several nonhistone acetylated substrates in budding yeast. Our approach, combined with more traditional experimental methods, may be useful for identifying acetylated substrates proteome-wide.