Department of Toxicology & Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari 48471-93698, Iran.
Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari 48167-75952, Iran.
Biomolecules. 2021 Feb 4;11(2):218. doi: 10.3390/biom11020218.
Arrestins are a small family of four proteins in most vertebrates that bind hundreds of different G protein-coupled receptors (GPCRs). Arrestin binding to a GPCR has at least three functions: precluding further receptor coupling to G proteins, facilitating receptor internalization, and initiating distinct arrestin-mediated signaling. The molecular mechanism of arrestin-GPCR interactions has been extensively studied and discussed from the "arrestin perspective", focusing on the roles of arrestin elements in receptor binding. Here, we discuss this phenomenon from the "receptor perspective", focusing on the receptor elements involved in arrestin binding and emphasizing existing gaps in our knowledge that need to be filled. It is vitally important to understand the role of receptor elements in arrestin activation and how the interaction of each of these elements with arrestin contributes to the latter's transition to the high-affinity binding state. A more precise knowledge of the molecular mechanisms of arrestin activation is needed to enable the construction of arrestin mutants with desired functional characteristics.
arrestins 是脊椎动物中一个由四个蛋白组成的小家族，它们可以结合数百种不同的 G 蛋白偶联受体 (GPCRs)。 arrestin 与 GPCR 的结合至少具有三种功能：阻止受体与 G 蛋白进一步偶联、促进受体内化以及启动不同的 arrestin 介导的信号转导。 arrestin-GPCR 相互作用的分子机制已从“ arrestin 视角”进行了广泛的研究和讨论，重点关注 arrestin 元件在受体结合中的作用。在这里，我们从“受体视角”讨论这一现象，重点讨论涉及 arrestin 结合的受体元件，并强调需要填补的现有知识空白。了解受体元件在 arrestin 激活中的作用以及这些元件中的每一个与 arrestin 的相互作用如何有助于 arrestin 向高亲和力结合状态的转变至关重要。为了构建具有所需功能特性的 arrestin 突变体，需要更精确地了解 arrestin 激活的分子机制。
