Systems Analysis of Protein Fatty Acylation in Herpes Simplex Virus-Infected Cells Using Chemical Proteomics.
Systems Analysis of Protein Fatty Acylation in Herpes Simplex Virus-Infected Cells Using Chemical Proteomics.
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DOI：
10.1016/j.chembiol.2015.06.024
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发表时间：
2015-08-20
影响因子：
--
通讯作者：
O'Hare P
中科院分区：
文献类型：
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作者：
Serwa RA;Abaitua F;Krause E;Tate EW;O'Hare P
蛋白质脂肪酰化调节细胞功能和组织的各个方面，并在宿主对感染的免疫反应中发挥关键作用。酰化也调节病毒编码蛋白的功能和定位。在这里，我们使用化学蛋白质组学工具、生物正交探针和捕获试剂来研究单纯疱疹病毒（HSV）感染过程中的肉豆肉酰化和棕榈酰化。通过凝胶内荧光成像和定量质谱分析，我们发现宿主蛋白的肉豆蔻酰化普遍降低，而宿主蛋白的棕榈酰化，包括干扰素和四白蛋白家族蛋白的调节因子，被选择性抑制。此外，我们发现病毒蛋白质组的很大一部分经历棕榈酰化；我们鉴定了许多病毒膜糖蛋白、结构蛋白和激酶。综上所述，我们的研究结果为HSV感染过程中的蛋白酰化提供了广泛的监督，为在其他系统中进行类似分析提供了路线图，并为进行系统和功能的具体分析提供了资源。宿主肉豆蔻酰化在棕榈酰化受到选择性影响的同时，在全球范围内降低宿主肉豆蔻酰化被选择性抑制的特异性宿主蛋白被鉴定出新的酰化病毒蛋白在复制过程中具有关键功能，Serwa等人为感染过程中蛋白质酰化的系统研究制定了路线图，以对一种大型复杂DNA病毒的分析为例。单纯疱疹病毒。利用生物正交探针和捕获试剂，作者量化了宿主酰化的变化，并鉴定了新的病毒编码的酰化蛋白。
Protein fatty acylation regulates diverse aspects of cellular function and organization and plays a key role in host immune responses to infection. Acylation also modulates the function and localization of virus-encoded proteins. Here, we employ chemical proteomics tools, bio-orthogonal probes, and capture reagents to study myristoylation and palmitoylation during infection with herpes simplex virus (HSV). Using in-gel fluorescence imaging and quantitative mass spectrometry, we demonstrate a generalized reduction in myristoylation of host proteins, whereas palmitoylation of host proteins, including regulators of interferon and tetraspanin family proteins, was selectively repressed. Furthermore, we found that a significant fraction of the viral proteome undergoes palmitoylation; we identified a number of virus membrane glycoproteins, structural proteins, and kinases. Taken together, our results provide broad oversight of protein acylation during HSV infection, a roadmap for similar analysis in other systems, and a resource with which to pursue specific analysis of systems and functions. High-throughput analysis of protein acylation during herpes virus infection described Host myristoylation is reduced globally while palmitoylation is affected selectively Specific host proteins whose palmitoylation is selectively repressed are identified New acylated viral proteins are identified with crucial functions during replication Serwa et al. develop a roadmap for the systematic investigation of protein acylation during infection, exemplified by analysis of a large complex DNA virus, herpes simplex virus. Using bio-orthogonal probes and capture reagents, the authors quantify alterations to host acylation and identify novel virus-encoded acylated proteins.