{Reference Type}: Journal Article
{Title}: Roles of the gate loop in β-arrestin-1 conformational dynamics and phosphorylated receptor interaction.
{Author}: Kim K;Ashim J;Ham D;Yu W;Chung KY;
{Journal}: Structure
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 7
{Factor}: 5.871
{DOI}: 10.1016/j.str.2024.05.014
{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.