Exploring protein lipidation with chemical biology.
Exploring protein lipidation with chemical biology.
复制标题
DOI：
10.1021/cr2001977
复制
发表时间：
2011-10-12
期刊：
影响因子：
62.1
通讯作者：
Linder, Maurine E.
中科院分区：
文献类型：
--
作者：
Hang, Howard C.;Linder, Maurine E.
蛋白质脂化是脂类基团与蛋白质的共价附着。脂质修饰大量真核蛋白并调节蛋白质的功能和定位。脂质修饰的疏水性使蛋白质脂化的研究具有挑战性。化学生物学通过新的检测和分离方法、抑制剂的设计和合成、监测细胞内脂化蛋白行为的策略以及生产用于结构和生物物理分析的脂化蛋白的方法，在推进蛋白质脂化领域发挥着越来越重要的作用。在这篇综述中，我们讨论了已经开发的化学工具，以促进蛋白质脂化领域的发现，并提供了一些例子，说明这些工具如何创造了对蛋白质脂化范围及其生物学后果的新认识。本综述的内容仅限于发生在细胞质或细胞膜细胞质表面的主要翻译后修饰：s -戊烯酰化、n -肉豆肉酰化和s -棕榈酰化（图1）。用于分泌的分子的蛋白质脂化发生在分泌途径内的细胞器管腔中。糖基磷脂酰肌醇（GPI）锚定物附着在内质网中的蛋白质上，将蛋白质拴在质膜的细胞外表面。其他脂化的分泌蛋白包括形态因子、细胞因子和激素。例子包括辛烷酰化肽激素ghrelin和Hedgehog信号蛋白，后者被胆固醇和棕榈酸酯修饰。发生在分泌细胞器腔内的脂质修饰在其他地方进行了综述。1
Protein lipidation is the covalent attachment of a lipid group to protein. Lipids modify large numbers of eukaryotic proteins and regulate protein function and localization. The hydrophobic character of lipid modifications makes the study of protein lipidation challenging. Chemical biology has played an increasingly important role in advancing the field of protein lipidation through novel methods of detection and isolation, design and synthesis of inhibitors, strategies to monitor the behavior of lipidated proteins in cells, and methods to produce lipidated proteins for structural and biophysical analyses. In this review, we discuss the chemical tools that have been developed to facilitate discovery in the field of protein lipidation and provide examples of how this has created new understanding of the scope of protein lipidation and its biological consequences.The content of this review is limited to the major posttranslational modifications that occur in the cytoplasm or on the cytoplasmic face of membranes: S-prenylation, N-myristoylation, and S-palmitoylation (Figure 1). Protein lipidation of molecules destined for secretion occurs in the lumen of organelles within the secretory pathway. Glycosylphosphatidylinositol (GPI) anchors attached to proteins in the endoplasmic reticulum tether proteins to the extracellular face of the plasma membrane. Other secreted proteins that are lipidated include morphogens, cytokines, and hormones. Examples include the octanoylated peptide hormone ghrelin and the Hedgehog signaling protein, which is modified with both cholesterol and palmitate. Lipid modifications that occur in the lumen of secretory organelles are reviewed elsewhere. 1
登录
查看更多内容
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：
5.3
作者：
Apolloni, A;Prior, IA;Hancock, JF
通讯作者：
Hancock, JF
影响因子：
14.8
作者：
Dekker, Frank J.;Rocks, Oliver;Waldmann, Herbert
通讯作者：
Waldmann, Herbert
DOI：
10.1074/jbc.m900519200
发表时间：
2009-06-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Dowen RH;Engel JL;Shao F;Ecker JR;Dixon JE
通讯作者：
Dixon JE
影响因子：
64.5
作者：
Choy, E;Chiu, VK;Philips, MR
通讯作者：
Philips, MR