Agonist-bound structures of G protein-coupled receptors

G protein-coupled receptors (GPCRs) play a major role in intercellular communication by binding small diffusible ligands (agonists) at the extracellular surface. Agonist-binding induces a conformational change in the receptor, which results in the binding and activation of heterotrimeric G proteins within the cell. Ten agonist-bound structures of non-rhodopsin GPCRs published last year defined for the first time the molecular details of receptor activated states and how inverse agonists, partial agonists and full agonists bind to produce different effects on the receptor. In addition, the structure of the β2-adrenoceptor coupled to a heterotrimeric G protein showed how the opening of a cleft in the cytoplasmic face of the receptor as a consequence of agonist binding results in G protein coupling and activation of the G protein.

► Structures have been determined of the β1 and β2 adrenoceptors and the adenosine A2A receptor bound to either full agonists or partial agonists. ► The first structure of a G protein-coupled receptor bound to a G protein has been determined. ► The structures identify conformational changes that occur in the receptors upon agonist binding and how these may activate a G protein.