Biased Signaling Pathways in β2-adrenergic Receptor Characterized by 19F-NMR

Overview

Journal Science

Specialty Science

Date 2012 Jan 24

PMID 22267580

Citations 330

Authors

Jeffrey J Liu

Reto Horst

Vsevolod Katritch

Raymond C Stevens

Kurt Wuthrich

Affiliations

Soon will be listed here.

Abstract

Extracellular ligand binding to G protein-coupled receptors (GPCRs) modulates G protein and β-arrestin signaling by changing the conformational states of the cytoplasmic region of the receptor. Using site-specific (19)F-NMR (fluorine-19 nuclear magnetic resonance) labels in the β(2)-adrenergic receptor (β(2)AR) in complexes with various ligands, we observed that the cytoplasmic ends of helices VI and VII adopt two major conformational states. Changes in the NMR signals reveal that agonist binding primarily shifts the equilibrium toward the G protein-specific active state of helix VI. In contrast, β-arrestin-biased ligands predominantly impact the conformational states of helix VII. The selective effects of different ligands on the conformational equilibria involving helices VI and VII provide insights into the long-range structural plasticity of β(2)AR in partial and biased agonist signaling.

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