Work

Biased Signaling Pathways in β 2 -Adrenergic Receptor Characterized by 19 F-NMR

Year: 2012

Type: article

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.

Source: Science

DOI: 10.1126/science.1215802

Authors: Jeffrey J. Liu, Reto Horst, Vsevolod Katritch, Raymond C. Stevens, Kurt Wüthrich

Institution: Scripps Research Institute

Language: English

Topic: Receptor Mechanisms and Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: JCIMPT-Complexes, GPCR Network