Roles of the gate loop in β-arrestin-1 conformational dynamics and phosphorylated receptor interaction,Structure

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Roles of the gate loop in β-arrestin-1 conformational dynamics and phosphorylated receptor interaction
Structure ( IF 4.4 ) Pub Date : 2024-06-17 , DOI: 10.1016/j.str.2024.05.014
Kiae Kim ₁ , Janbolat Ashim ₂ , Donghee Ham ₁ , Wookyung Yu ₂ , Ka Young Chung ₁

Affiliation

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.

中文翻译：

门环在 β-arrestin-1 构象动力学和磷酸化受体相互作用中的作用

抑制蛋白与磷酸化 G 蛋白偶联受体 (GPCR) 相互作用并调节 GPCR 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-arrestin-1 和 2 型加压素受体 (V2Rpp) 磷酸化 C 尾肽作为模型系统，研究了门环中特定残基（K292、K294 和 H295）的作用。我们测量了 V2Rpp 的结合亲和力并分析了 β-arrestin-1 的构象动力学。我们的结果表明，K294 在与 V2Rpp 的相互作用中发挥着关键作用，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。

更新日期：2024-06-17

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