The amino terminus of Galpha(z) is required for receptor recognition, whereas its alpha4/beta6 loop is essential for inhibition of adenylyl cyclase.

G(z) couples to most of the known G(i)-linked receptors and its alpha subunit (Galpha(z)) inhibits adenylyl cyclases as efficiently as Galpha(i) subtypes. A series of chimeric Galpha subunits with different portions of Galpha(z) and Galpha(t1) (a regulator of cGMP phosphodiesterase) were constructed to study the essential structural elements of Galpha(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 betagamma subunits from the chimeras, and 2) inhibition of isoproterenol-stimulated adenylyl cyclase by the chimeric Galpha subunits. The results suggested that the presence of both termini of Galpha(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 alpha4/beta6 loop was identified as one of the adenylyl cyclase inhibitory domains of Galpha(z).