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

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Science  02 Mar 2012:
Vol. 335, Issue 6072, pp. 1106-1110
DOI: 10.1126/science.1215802

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The β2-adrenergic receptor (β2AR) is a G protein–coupled receptor that recognizes diverse ligands to trigger signaling in the cell. Besides binding G proteins, activated β2AR can be phosphorylated and bind arrestin, which redirects signaling to other pathways. Some β2AR ligands are “biased” in that they differentially activate G protein or arrestin signaling. Liu et al. (p. 1106, published online 19 January; see the Perspective by Sprang and Chief Elk) used 19F-NMR spectroscopy to examine conformational changes associated with a range of ligands and discovered that biased ligands caused differential shifts in equilibrium between two conformational states—the G protein binding state and the arrestin binding state—and thus provide a basis for rational design of pharmacological ligands.