Pejman Ghanouni

Publication Details

  • Agonists induce conformational changes in transmembrane domains III and VI of the beta(2) adrenoceptor EMBO JOURNAL Gether, U., Lin, S., Ghanouni, P., Ballesteros, J. A., Weinstein, H., Kobilka, B. K. 1997; 16 (22): 6737-6747


    Agonist binding to G protein-coupled receptors is believed to promote a conformational change that leads to the formation of the active receptor state. However, the character of this conformational change which provides the important link between agonist binding and G protein coupling is not known. Here we report evidence that agonist binding to the beta2 adrenoceptor induces a conformational change around 125Cys in transmembrane domain (TM) III and around 285Cys in TM VI. A series of mutant beta2 adrenoceptors with a limited number of cysteines available for chemical derivatization were purified, site-selectively labeled with the conformationally sensitive, cysteine-reactive fluorophore IANBD and analyzed by fluorescence spectroscopy. Like the wild-type receptor, mutant receptors containing 125Cys and/or 285Cys showed an agonist-induced decrease in fluorescence, while no agonist-induced response was observed in a receptor where these two cysteines were mutated. These data suggest that IANBD bound to 125Cys and 285Cys are exposed to a more polar environment upon agonist binding, and indicate that movements of transmembrane segments III and VI are involved in activation of G protein-coupled receptors.

    View details for Web of Science ID A1997YJ20700013

    View details for PubMedID 9362488

Stanford Medicine Resources:

Footer Links: