Abstract：
Arrestins interact with phosphorylated G protein-coupled receptors (GPCRs) and regulate the homologous desensitization and internalization of GPCRs. The gate loop in arrestins is a critical region for both stabilization of the basal state and interaction with phosphorylated receptors. We investigated the roles of specific residues in the gate loop (K292, K294, and H295) using β-arrestin-1 and phosphorylated C-tail peptide of vasopressin receptor type 2 (V2Rpp) as a model system. We measured the binding affinity of V2Rpp and analyzed conformational dynamics of β-arrestin-1. Our results suggest that K294 plays a critical role in the interaction with V2Rpp without influencing the overall conformation of the V2Rpp-bound state. The residues K292 and H295 contribute to the stability of the polar core in the basal state and form a specific conformation of the finger loop in the V2Rpp-bound state.
摘要：
抑制蛋白与磷酸化G蛋白偶联受体（GPCRs）相互作用，并调节GPCRs的同源脱敏和内化。抑制蛋白中的门环是稳定基础状态和与磷酸化受体相互作用的关键区域。我们使用β-抑制蛋白1和2型血管加压素受体（V2Rpp）的磷酸化C尾肽作为模型系统，研究了门环（K292，K294和H295）中特定残基的作用。我们测量了V2Rpp的结合亲和力并分析了β-抑制蛋白-1的构象动力学。我们的结果表明，K294在与V2Rpp的相互作用中起关键作用，而不影响V2Rpp结合状态的整体构象。残基K292和H295有助于极性核心在基础状态下的稳定性，并在V2Rpp结合状态下形成指环的特定构象。
