Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
Int J Mol Sci. 2021 Nov 19;22(22):12481. doi: 10.3390/ijms222212481.
Arrestins are a small family of proteins that bind G protein-coupled receptors (GPCRs). Arrestin binds to active phosphorylated GPCRs with higher affinity than to all other functional forms of the receptor, including inactive phosphorylated and active unphosphorylated. The selectivity of arrestins suggests that they must have two sensors, which detect receptor-attached phosphates and the active receptor conformation independently. Simultaneous engagement of both sensors enables arrestin transition into a high-affinity receptor-binding state. This transition involves a global conformational rearrangement that brings additional elements of the arrestin molecule, including the middle loop, in contact with a GPCR, thereby stabilizing the complex. Here, we review structural and mutagenesis data that identify these two sensors and additional receptor-binding elements within the arrestin molecule. While most data were obtained with the arrestin-1-rhodopsin pair, the evidence suggests that all arrestins use similar mechanisms to achieve preferential binding to active phosphorylated GPCRs.
抑制蛋白是一小类与 G 蛋白偶联受体（GPCR）结合的蛋白质。与所有其他功能性受体形式（包括非磷酸化失活和磷酸化激活的受体）相比，抑制蛋白与活性磷酸化 GPCR 的结合亲和力更高。抑制蛋白的选择性表明它们必须具有两个传感器，分别检测受体结合的磷酸基团和活性受体构象。两个传感器的同时参与使抑制蛋白转变为高亲和力受体结合状态。这种转变涉及到全局构象重排，使抑制蛋白分子的其他元件（包括中间环）与 GPCR 接触，从而稳定复合物。在这里，我们回顾了结构和突变体数据，这些数据确定了抑制蛋白分子中的这两个传感器和其他受体结合元件。虽然大多数数据是使用抑制蛋白-1-视紫红质对获得的，但有证据表明，所有抑制蛋白都使用类似的机制来优先结合活性磷酸化的 GPCR。
