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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Proteome-wide prediction of acetylation substrates
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Proteome-wide prediction of acetylation substrates

机译：蛋白质组学预测乙酰化底物

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摘要

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.
机译：乙酰化是经过充分研究的翻译后修饰，已与广泛的生物学过程相关，尤其是基因调控。许多研究为我们对乙酰化基础酶学的知识做出了贡献，包括努力了解几种乙酰基转移酶识别底物的分子机制，但是确定底物位点特异性的内在特征的传统实验已证明具有挑战性。在这里，我们将实验方法与蛋白质序列的聚类分析相结合，以利用我们独特的预测工具PredMod基于组蛋白内乙酰化赖氨酸的序列特征来预测蛋白质乙酰化。我们通过实施组蛋白和非组蛋白序列的聚类分析，定义了代表潜在乙酰化位点的局部氨基酸序列组成。我们显示此序列组成对乙酰化标记的2个独立实验数据集具有预测能力。最后，我们使用质谱检测选定推定底物的乙酰化，并报告出芽酵母中几种非组蛋白乙酰化的底物。我们的方法与更传统的实验方法相结合，可能有助于在整个蛋白质组学范围内鉴定乙酰化底物。

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    Amrita Basu; Kristie L. Rose; Junmei Zhang; Ronald C. Beavis; Beatrix Ueberheide; Benjamin A. Garcia; Brian Chait; Yingming Zhao; Donald F. Hunt; Eran Segal; C. David Allis; Sandra B. Hake;

  • 作者单位

    Laboratory of Chromatin Biology, Rockefeller University, New York, NY 10065;

    Departments of Chemistry and Pathology, University of Virginia, McCormick Road, Charlottesville, VA 22904;

    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390;

    Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 123;

    Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, New York, NY 10065;

    Department of Molecular Biology, Princeton University, Princeton, NJ 08544;

    Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, New York, NY 10065;

    Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637;

    Departments of Chemistry and Pathology, University of Virginia, McCormick Road, Charlottesville, VA 22904;

    Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel;

    Laboratory of Chromatin Biology, Rockefeller University, New York, NY 10065;

    Department of Molecular Biology, Adolf-Butenandt-lnstitut and Center for Integrated Protein Science Munich, Ludwig Maximilian Universitat 80336, Munich, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    histone; nonhistone; prediction; acetylation; PredMod;

    机译：组蛋白非组蛋白预测;乙酰化PredMod;

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