The amino terminus of Gαz is required for receptor recognition, whereas its α4/β6 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) subtypes. A series of chimeric G alpha subunits with different portions of G alpha(z) and G alpha(t1) (a regulator of cGMP phosphodiesterase) were constructed to study the essential structural elements of G alpha(z) that determine receptor coupling and effector interaction. The receptor-mediated functions of the chimeras were assessed in two aspects: 1) stimulation of type 2 adenylyl cyclase through the release of beta gamma subunits from the chimeras, and 2) inhibition of isoproterenol-stimulated adenylyl cyclase by the chimeric G alpha subunits. The results suggested that the presence of both termini 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 acids (295-319) corresponding to the alpha 4/beta 6 loop was identified as one of the adenylyl cyclase inhibitory domains of G alpha(z).