An arginine switch drives the stepwise activation of β-arrestin by CXCR7.

ABSTRACT: β-arrestins (βarrs) play a crucial role in regulating G protein-coupled receptor (GPCR) signaling and trafficking. Canonically, interactions of βarr with the phosphorylated intracellular GPCR-tail induce a multi-step conformational transition that results in the activation of βarr. Depending on the specific interaction pattern with the receptor, βarrs adopt multiple conformational states, each tightly linked to a specific functional outcome of βarr recruitment. Despite its physiological relevance, the structural determinants of βarr activation remain poorly understood. Using a combination of molecular dynamics simulations, biochemical and cell-based experiments, we reveal how specific interactions with a chemokine receptor 7 (CXCR7) promote the unbinding of the βarr2 C-tail-a crucial step

SUBMITTER: Ji JS 

PROVIDER: S-EPMC12331092 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature