Agonists induce conformational changes in transmembrane domains III and VI of the beta 2 adrenoceptor

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