Emerging technologies to map the protein methylome.
Emerging technologies to map the protein methylome.
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DOI：
10.1016/j.jmb.2014.04.024
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发表时间：
2014-10-09
影响因子：
5.6
通讯作者：
Gozani O
中科院分区：
文献类型：
--
作者：
Carlson SM;Gozani O
蛋白质甲基化在细胞信号中发挥着不可或缺的作用，最显著的是通过调节结合在染色质上的蛋白质，以及越来越多地通过调节非组蛋白蛋白质。理解甲基化如何在信号传递中起作用的一个核心挑战是识别和测量蛋白质甲基化。这包括对组蛋白、单个非组蛋白蛋白和整个蛋白质组的位点特异性修饰。传统上研究蛋白质甲基化的候选方法包括甲基化特异性抗体、翻译后修饰的质谱图和放射性标记来表征目标蛋白质上的甲基化。最近的发展提供了新的方法来识别甲基化蛋白，测量甲基化水平，识别甲基转移酶的底物，并将甲基化蛋白与甲基特定的阅读器结构域相匹配。甲基结合蛋白结构域和针对甲基化蛋白具有广泛特异性的改良抗体正被用于表征“蛋白质甲基组”。它们还有可能用于高通量分析，用于抑制剂筛选和药物开发。这些工具经常与改进的质谱学相结合，以快速识别甲基化残留物，并与蛋白质微阵列结合，在蛋白质微阵列中，它们可以用于筛选甲基化蛋白质。最后，新的化学生物学策略正被用来探索甲基转移酶、去甲基酶和甲基结合的“阅读器”结构域的功能。这些工具正在创建对蛋白质甲基化的“系统级”理解，并将蛋白质甲基化整合到更广泛的信号过程中。
Protein methylation plays an integral role in cellular signaling, most notably by modulating proteins bound at chromatin, and increasingly through regulation of non-histone proteins. One central challenge in understanding how methylation acts in signaling is identifying and measuring protein methylation. This includes locus-specific modification of histones, on individual non-histone proteins, and globally across the proteome. Protein methylation has traditionally been studied using candidate approaches such as methylation-specific antibodies, mapping of post-translational modifications by mass spectrometry, and radioactive labeling to characterize methylation on target proteins. Recent developments have provided new approaches to identify methylated proteins, measure methylation levels, identify substrates of methyltransferase enzymes, and match methylated proteins to methyl-specific reader domains. Methyl-binding protein domains and improved antibodies with broad specificity for methylated proteins are being used to characterize the “protein methylome”. They also have the potential to be used in high-throughput assays for inhibitor screens and drug development. These tools are often coupled to improvements in mass spectrometry to quickly identify methylated residues, and to protein microarrays, where they can be used to screen for methylated proteins. Finally, new chemical biology strategies are being used to probe the function of methyltransferases, demethylases and methyl-binding “reader” domains. These tools are creating a “system-level” understanding of protein methylation, and integrating protein methylation into broader signaling processes.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
16
作者：
Banko, Max R.;Allen, Jasmina J.;Schaffer, Bethany E.;Wilker, Erik W.;Tsou, Peiling;White, Jamie L.;Villen, Judit;Wang, Beatrice;Kim, Sara R.;Sakamoto, Kei;Gygi, Steven P.;Cantley, Lewis C.;Yaffe, Michael B.;Shokat, Kevan M.;Brunet, Anne
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影响因子：
46.9
作者：
Ficarro, SB;McCleland, ML;White, FM
通讯作者：
White, FM
DOI：
10.1073/pnas.0708966105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Blethrow, Justin D.;Glavy, Joseph S.;Shokat, Kevan M.
通讯作者：
Shokat, Kevan M.
影响因子：
7
作者：
Fisk, John C.;Li, Jun;Read, Laurie K.
通讯作者：
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