Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
Prog Mol Biol Transl Sci. 2013;118:57-92. doi: 10.1016/B978-0-12-394440-5.00003-6.
Arrestins are a small protein family with only four members in mammals. Arrestins demonstrate an amazing versatility, interacting with hundreds of different G protein-coupled receptor (GPCR) subtypes, numerous nonreceptor signaling proteins, and components of the internalization machinery, as well as cytoskeletal elements, including regular microtubules and centrosomes. Here, we focus on the structural determinants that mediate various arrestin functions. The receptor-binding elements in arrestins were mapped fairly comprehensively, which set the stage for the construction of mutants targeting particular GPCRs. The elements engaged by other binding partners are only now being elucidated and in most cases we have more questions than answers. Interestingly, even very limited and imprecise identification of structural requirements for the interaction with very few other proteins has enabled the development of signaling-biased arrestin mutants. More comprehensive understanding of the structural underpinning of different arrestin functions will pave the way for the construction of arrestins that can link the receptor we want to the signaling pathway of our choosing.
arrestins 是一个仅有四个成员的小蛋白家族。 arrestins 表现出惊人的多功能性，与数百种不同的 G 蛋白偶联受体 (GPCR) 亚型、许多非受体信号蛋白以及内化机制的成分以及细胞骨架元素（包括常规微管和中心体）相互作用。在这里，我们专注于介导各种 arrestin 功能的结构决定因素。 arrestins 中的受体结合元件已被相当全面地定位，这为构建针对特定 GPCR 的突变体奠定了基础。其他结合伙伴结合的元件现在才刚刚被阐明，在大多数情况下，我们的问题多于答案。有趣的是，即使对与极少数其他蛋白质相互作用的结构要求进行非常有限和不精确的识别，也能够开发出偏向信号的 arrestin 突变体。对不同 arrestin 功能的结构基础的更全面理解将为构建能够将我们想要的受体与我们选择的信号通路联系起来的 arrestin 铺平道路。
