G protein coupled receptors (GPCR) represent one of the largest families of integral membrane proteins and are responsible for the majority transmembrane signal transduction. GPCRs share a common structural motif consisting of 7 membrane spanning domains with an extracellular amino terminus and intracellular carboxyl terminus. Much of what we know about the structure of G protein coupled receptors comes from studies on rhodopsin, a special member of the GPCR family capable of detecting a single photon. The beta 2 adrenergic receptor (beta 2AR) is the first ligand-activated G protein coupled receptor (GPCR) to be cloned and one of the best characterized members of this large family of integral membrane proteins. It serves as a paradigm for GPCR activation and regulation. My lab has a long-standing interest in understanding the structure and mechanism of action of the beta 2 AR. The proposed studies are designed to elucidate the mechanism by which agonist binding leads to G protein activation. We will use biophysical techniques to directly monitor ligand- and G protein-induced conformational changes in purified beta 2 AR in real- time.
The Specific Aims i nclude: 1. To characterize ligand-induced conformational changes in the beta 2 AR. 2. To determine the effect of beta 2 AR-Gs coupling on receptor structure and response to ligands. 3. To identify distinct conformational studies in the beta 2 AR.
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