Conformational signatures in β-arrestin2 reveal natural biased agonism at a G-protein-coupled receptor.

ABSTRACT: Discovery of biased ligands and receptor mutants allows characterization of G-protein- and β-arrestin-mediated signaling mechanisms of G-protein-coupled receptors (GPCRs). However, the structural mechanisms underlying biased agonism remain unclear for many GPCRs. We show that while Galanin induces the activation of the galanin receptor 2 (Galr2) that leads to a robust stimulation toward Gαq-protein and β-arrestin1/2, an alternative ligand Spexin and its analog have biased agonism toward G-protein signaling relative to Galanin. We used intramolecular fluorescein arsenical hairpin bioluminescence resonance energy transfer-based biosensors of β-arrestin2 combined with NanoBit technology to measure β-arrestin2-Galr2 interactions in real-time living systems. We found that Spexin and Galanin ind

SUBMITTER: Reyes-Alcaraz A 

PROVIDER: S-EPMC6123711 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature