用化学报告物对哺乳动物细胞中脂肪酸酰化蛋白的蛋白质组学分析揭示了组蛋白 H3 变体的 S-酰化。
Proteomic analysis of fatty-acylated proteins in mammalian cells with chemical reporters reveals S-acylation of histone H3 variants.
机构信息
The Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY 10065, USA.
出版信息
Mol Cell Proteomics. 2011 Mar;10(3):M110.001198. doi: 10.1074/mcp.M110.001198. Epub 2010 Nov 14.
Abstract
Bioorthogonal chemical reporters are useful tools for visualizing and identifying post-translational modifications on proteins. Here we report the proteomic analysis of mammalian proteins targeted by a series of fatty acid chemical reporters ranging from myristic to stearic acid. The large-scale analysis of total cell lysates from fully solubilized Jurkat T cells identified known fatty-acylated proteins and many new candidates, including nuclear proteins and in particular histone H3 variants. We demonstrate that histones H3.1, H3.2, and H3.3 are modified with fatty acid chemical reporters and identify the conserved cysteine 110 as a new site of S-acylation on histone H3.2. This newly discovered modification of histone H3 could have implications for nuclear organization and chromatin regulation. The unbiased proteomic analysis of fatty-acylated proteins using chemical reporters has revealed a greater diversity of lipid-modified proteins in mammalian cells and identified a novel post-translational modification of histones.
摘要
生物正交化学报告物是用于可视化和鉴定蛋白质翻译后修饰的有用工具。在这里，我们报告了一系列从豆蔻酸到硬脂酸的脂肪酸化学报告物靶向的哺乳动物蛋白质的蛋白质组学分析。对完全溶解的 Jurkat T 细胞总细胞裂解物的大规模分析鉴定了已知的脂肪酸酰化蛋白和许多新的候选蛋白，包括核蛋白，特别是组蛋白 H3 变体。我们证明组蛋白 H3.1、H3.2 和 H3.3 被脂肪酸化学报告物修饰，并确定保守的半胱氨酸 110 是组蛋白 H3 上 S 酰化的新位点。组蛋白 H3 的这种新发现的修饰可能对核组织和染色质调节有影响。使用化学报告物对脂肪酸酰化蛋白进行的无偏蛋白质组学分析揭示了哺乳动物细胞中脂质修饰蛋白的更大多样性，并鉴定了组蛋白的一种新的翻译后修饰。
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