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

The G protein betagamma complex modulates the function of a variety of effectors in biological signaling. However, the individual roles of the beta and gamma subunits in this interaction are unknown. Unlike in the case of the alpha subunit, domains on the betagamma complex that contact effectors have not yet been identified. We show here using the yeast two-hybrid system that the beta subunit and not the gamma subunit interacts with domains specific to adenylyl cyclase type 2 (AC2) and the muscarinic receptor-gated atrial inwardly rectifying potassium channel, GIRK1. Different beta 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 beta subunit. This domain includes the region where the beta subunit contacts with the alpha subunit in the crystal structure and may therefore explain the ability of the alpha subunit to shut off the activity of the betagamma complex.