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Nouroddin Sotoudeh Chafi

Posted on January 25, 2017


Date - January 25, 2017
1:00 pm


Ph.D. Literature Seminar – 751
Title: “The Dynamic Process of b2-Adrenergic Receptor Activation”


G-protein-coupled receptors (GPCRs) can modulate diverse signaling pathways, often in a ligand-specific manner. The full range of functionally relevant GPCR conformations is poorly understood. The researchers use NMR spectroscopy to characterize the conformational dynamics of the transmembrane core of the b2 -adrenergic receptor (b2-AR), a prototypical GPCR. They labeled b2-AR with CH3 -Methionine and obtained HSQC spectra of unliganded receptor as well as receptor bound to an inverse agonist, an agonist, and a G-protein-mimetic nanobody. These studies provide evidence for conformational states not observed in crystal structures, as well as substantial conformational heterogeneity in agonist and inverse-agonist-bound preparations. They also show that for b2-AR, unlike rhodopsin, an agonist alone does not stabilize a fully active conformation, suggesting that the conformational link between the agonist-binding pocket and the G-protein coupling surface is not rigid. The observed heterogeneity may be important for b2-AR’s ability to  engage multiple signaling and regulatory proteins.