The amino terminus of G alpha(z) is required for receptor recognition, whereas its alpha 4/beta 6 loop is essential for inhibition of adenylyl cyclase

G(z) couples to most of the known G(i)-linked receptors and its a subunit ( G alpha(z)) inhibits adenylyl cyclases as efficiently as G alpha(i) subtype s. A series of chimeric G alpha subunits with different portions of G alpha (z) and G alpha(t1) (a regulator of cGMP phosphodiesterase) were constructe d to study the essential structural elements of G alpha(z) that determine r eceptor coupling and effector interaction. The receptor-mediated functions of the chimeras were assessed in two aspects: 1) stimulation of type 2 aden ylyl cyclase through the release of beta gamma subunits from the chimeras, and 2) inhibition of isoproterenol-stimulated adenylyl cyclase by the chime ric G alpha subunits. The results suggested that the presence of both termi ni of G(alpha z) were critical for coupling to delta-opioid receptor, with the N-terminal region being more important. Moreover, a stretch of amino ac ids (295-319) corresponding to the alpha 4/beta 6 loop was identified as on e of the adenylyl cyclase inhibitory domains of G alpha(z).