Goth Christoffer K, Petäjä-Repo Ulla E, Rosenkilde Mette M
Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK 2200, Denmark.
Medical Research Center Oulu, Research Unit of Biomedicine, University of Oulu, Oulu, FI-90014, Finland.
ACS Pharmacol Transl Sci. 2020 Mar 17;3(2):237-245. doi: 10.1021/acsptsci.0c00016. eCollection 2020 Apr 10.
Post-translational modifications (PTMs) are a fundamental phenomenon across all classes of life and several hundred different types have been identified. PTMs contribute widely to the biological functions of proteins and greatly increase their diversity. One important class of proteins regulated by PTMs, is the cell surface expressed G protein-coupled receptors (GPCRs). While most PTMs have been shown to exert distinct biological functions, we are only beginning to approach the complexity that the potential interplay between different PTMs may have on biological functions and their regulation. Importantly, PTMs and their potential interplay represent an appealing mechanism for cell and tissue specific regulation of GPCR function and may partially contribute to functional selectivity of some GPCRs. In this review we highlight examples of PTMs located in GPCR extracellular domains, with special focus on glycosylation and the potential interplay with other close-by PTMs such as tyrosine sulfation, proteolytic cleavage, and phosphorylation.
翻译后修饰（PTMs）是所有生命类别中普遍存在的一种基本现象，目前已鉴定出数百种不同类型。PTMs广泛影响蛋白质的生物学功能，并极大地增加了其多样性。一类重要的受PTMs调节的蛋白质是细胞表面表达的G蛋白偶联受体（GPCRs）。虽然大多数PTMs已被证明具有独特的生物学功能，但我们才刚刚开始探究不同PTMs之间潜在的相互作用对生物学功能及其调节可能产生的复杂性。重要的是，PTMs及其潜在的相互作用代表了一种对GPCR功能进行细胞和组织特异性调节的有吸引力的机制，并且可能部分促成了某些GPCR的功能选择性。在本综述中，我们重点介绍位于GPCR细胞外结构域的PTMs实例，特别关注糖基化以及与其他相邻PTMs（如酪氨酸硫酸化、蛋白水解切割和磷酸化）的潜在相互作用。
