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.

中文翻译：

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蛋白质S-酰化的生理学。

蛋白质 S-酰化是唯一完全可逆的蛋白质翻译后脂质修饰，正在成为一种普遍存在的机制，可控制多种蛋白质的特性和功能，从而控制生理过程。S-酰化是长链脂质（最典型的是棕榈酸酯）通过不稳定的硫酯键加到可溶性和跨膜蛋白的细胞内半胱氨酸残基上而产生的。添加脂质会导致蛋白质疏水性增加，从而影响蛋白质结构、组装、成熟、运输和功能。由于改进了测定 S- 酰化的生化工具，以及最近发现的控制蛋白质 S- 酰化和去酰化的酶，最近全球 S-酰化（棕榈酰）蛋白质组学分析的爆炸式增长，为S-酰化的生理功能开辟了新的视野。这篇综述介绍了 S-酰化的关键特征和研究该过程的工具，并重点介绍了各种受调控的蛋白质，包括膜受体、离子通道和转运蛋白、酶和激酶、信号转导接头和伴侣、细胞粘附和结构蛋白。我们重点介绍了将 S-酰化破坏与病理生理学和疾病相关联的最新发现，并讨论了这个快速发展的领域中的一些主要挑战和机遇。信号适配器和伴侣、细胞粘附和结构蛋白。我们重点介绍了将 S-酰化破坏与病理生理学和疾病相关联的最新发现，并讨论了这个快速发展的领域中的一些主要挑战和机遇。信号适配器和伴侣、细胞粘附和结构蛋白。我们重点介绍了将 S-酰化破坏与病理生理学和疾病相关联的最新发现，并讨论了这个快速发展的领域中的一些主要挑战和机遇。