Helix-bundle and C-terminal GPCR domains differentially influence GRK-specific functions and β-arrestin-mediated regulation.

ABSTRACT: G protein-coupled receptors (GPCRs) orchestrate diverse physiological responses via signaling through G proteins, GPCR kinases (GRKs), and arrestins. While most G protein functions are well-established, the contributions of GRKs and arrestins remain incompletely understood. Here, we investigate the influence of β-arrestin-interacting GPCR domains (helix-bundle/C-terminus) on β-arrestin conformations and functions using refined biosensors and advanced cellular knockout systems. Focusing on prototypical class A (b2AR) and B (V2R) receptors and their chimeras (b2V2/V2b2), we show that most N-domain β-arrestin conformational changes are mediated by receptor C-terminus-interactions, while C-domain conformations respond to the helix-bundle or an individual combination of interaction interfaces.

SUBMITTER: Matthees ESF 

PROVIDER: S-EPMC12214593 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature