Chamberlain Luke H, Shipston Michael J
Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde University, Glasgow, United Kingdom; and Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Physiol Rev. 2015 Apr;95(2):341-76. doi: 10.1152/physrev.00032.2014.
Protein S-acylation, the only fully reversible posttranslational lipid modification of proteins, is emerging as a ubiquitous mechanism to control the properties and function of a diverse array of proteins and consequently physiological processes. S-acylation results from the enzymatic addition of long-chain lipids, most typically palmitate, onto intracellular cysteine residues of soluble and transmembrane proteins via a labile thioester linkage. Addition of lipid results in increases in protein hydrophobicity that can impact on protein structure, assembly, maturation, trafficking, and function. The recent explosion in global S-acylation (palmitoyl) proteomic profiling as a result of improved biochemical tools to assay S-acylation, in conjunction with the recent identification of enzymes that control protein S-acylation and de-acylation, has opened a new vista into the physiological function of S-acylation. This review introduces key features of S-acylation and tools to interrogate this process, and highlights the eclectic array of proteins regulated including membrane receptors, ion channels and transporters, enzymes and kinases, signaling adapters and chaperones, cell adhesion, and structural proteins. We highlight recent findings correlating disruption of S-acylation to pathophysiology and disease and discuss some of the major challenges and opportunities in this rapidly expanding field.
蛋白质S-酰化是蛋白质唯一完全可逆的翻译后脂质修饰，正逐渐成为一种普遍存在的机制，用于控制各种蛋白质的特性和功能，进而调控生理过程。S-酰化是通过不稳定的硫酯键，将长链脂质（最典型的是棕榈酸酯）酶促添加到可溶性和跨膜蛋白的细胞内半胱氨酸残基上的结果。脂质的添加会导致蛋白质疏水性增加，这可能会影响蛋白质的结构、组装、成熟、运输和功能。由于用于检测S-酰化的生化工具得到改进，以及最近对控制蛋白质S-酰化和去酰化的酶的鉴定，全球范围内蛋白质S-酰化（棕榈酰化）蛋白质组学分析的迅速发展，为S-酰化的生理功能开启了新的视野。本综述介绍了S-酰化的关键特征以及研究这一过程的工具，并重点介绍了一系列受调控的蛋白质，包括膜受体、离子通道和转运蛋白、酶和激酶、信号转导衔接蛋白和分子伴侣、细胞黏附蛋白以及结构蛋白。我们强调了最近将S-酰化破坏与病理生理学和疾病相关联的研究结果，并讨论了这个迅速发展的领域中的一些主要挑战和机遇。
