A domain on the G protein β subunit interacts with both adenylyl cyclase 2 and the muscarinic atrial potassium channel

The G protein βγ complex modulates the function of a variety of effectors in biological signaling. However, the individual roles of the β and γ subunits in this interaction are unknown. Unlike in the case of the α subunit, domains on the βγ complex that contact effectors have not yet been identified. We show here using the yeast two-hybrid system that the β subunit and not the γ subunit interacts with domains specific to adenylyl cyclase type 2 (AC2) and the muscarinic receptor-gated atrial inwardly rectifying potassium channel, GIRK1. Different β subunit types interact with these effector domains with different efficacies. Furthermore, an N-terminal fragment of 100 residues interacts with both these effector domains as effectively as the whole β subunit. This domain includes the region where the β subunit contacts with the α subunit in the crystal structure and may therefore explain the ability of the α subunit to shut off the activity of the βγ complex.