Chemoproteomics reveals Toll-like receptor fatty acylation.
Chemoproteomics reveals Toll-like receptor fatty acylation.
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DOI：
10.1186/s12915-014-0091-3
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发表时间：
2014-11-05
期刊：
影响因子：
5.4
通讯作者：
Yount JS
中科院分区：
文献类型：
--
作者：
Chesarino NM;Hach JC;Chen JL;Zaro BW;Rajaram MV;Turner J;Schlesinger LS;Pratt MR;Hang HC;Yount JS
棕榈酰化是一种16碳脂质的翻译后修饰，可增加蛋白质的疏水性。这种形式的蛋白质脂肪酰化正在成为细胞相互作用和信号传导多个方面的关键调控修饰。尽管最近在快速鉴定和可视化棕榈酰化蛋白的化学工具的发展方面取得了进展，但棕榈酰蛋白质组尚未完全定义。在这里，我们试图鉴定和比较小鼠成纤维细胞和树突状细胞中的棕榈酰化蛋白。总共鉴定了563个假定的棕榈酰化底物，其中200多个在过去的蛋白质组学研究中没有被认为是棕榈酰化的。在这里，我们验证了几种新蛋白的棕榈酰化，包括toll样受体（TLRs） 2、5和10、CD80、CD86和NEDD4。TLR2的棕榈酰化是树突状细胞中唯一鉴定的，被定位为跨膜结构域-近端半胱氨酸。通过药物或半胱氨酸诱变抑制TLR2 s -棕榈酰化导致细胞表面表达降低和对微生物配体的炎症反应降低。这项工作鉴定了许多参与基本细胞过程和细胞类型特异性功能的脂肪酰化蛋白，突出了检测多种细胞类型的棕榈酰蛋白质组的价值。TLR2的s -棕榈酰化是一种以前未知的免疫调节机制，它代表了TLR2炎症活性调节的一种全新途径。本文的在线版本（doi:10.1186/s12915-014-0091-3）包含补充材料，可供授权用户使用。
Palmitoylation is a 16-carbon lipid post-translational modification that increases protein hydrophobicity. This form of protein fatty acylation is emerging as a critical regulatory modification for multiple aspects of cellular interactions and signaling. Despite recent advances in the development of chemical tools for the rapid identification and visualization of palmitoylated proteins, the palmitoyl proteome has not been fully defined. Here we sought to identify and compare the palmitoylated proteins in murine fibroblasts and dendritic cells. A total of 563 putative palmitoylation substrates were identified, more than 200 of which have not been previously suggested to be palmitoylated in past proteomic studies. Here we validate the palmitoylation of several new proteins including Toll-like receptors (TLRs) 2, 5 and 10, CD80, CD86, and NEDD4. Palmitoylation of TLR2, which was uniquely identified in dendritic cells, was mapped to a transmembrane domain-proximal cysteine. Inhibition of TLR2 S-palmitoylation pharmacologically or by cysteine mutagenesis led to decreased cell surface expression and a decreased inflammatory response to microbial ligands. This work identifies many fatty acylated proteins involved in fundamental cellular processes as well as cell type-specific functions, highlighting the value of examining the palmitoyl proteomes of multiple cell types. S-palmitoylation of TLR2 is a previously unknown immunoregulatory mechanism that represents an entirely novel avenue for modulation of TLR2 inflammatory activity. The online version of this article (doi:10.1186/s12915-014-0091-3) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
Charron G;Tsou LK;Maguire W;Yount JS;Hang HC
通讯作者：
Hang HC
影响因子：
4.8
作者：
Fukata, Yuko;Iwanaga, Tsuyoshi;Fukata, Masaki
通讯作者：
Fukata, Masaki
影响因子：
56.9
作者：
FREEMAN, GJ;GRIBBEN, JG;NADLER, LM
通讯作者：
NADLER, LM
影响因子：
3.7
作者：
Brandt KJ;Fickentscher C;Kruithof EK;de Moerloose P
通讯作者：
de Moerloose P
影响因子：
4
作者：
Davda D;El Azzouny MA;Tom CT;Hernandez JL;Majmudar JD;Kennedy RT;Martin BR
通讯作者：
Martin BR