A DOMAIN ON THE G-PROTEIN BETA-SUBUNIT INTERACTS WITH BOTH ADENYLYL-CYCLASE-2 AND THE MUSCARINIC ATRIAL POTASSIUM CHANNEL

The G protein beta gamma complex modulates the function of a variety o f effecters 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 beta gamma complex that contact effecters have not yet been identified. We show here using th e yeast two-hybrid system that the beta subunit and not the gamma subu nit interacts with domains specific to adenylyl cyclase type 2 (AC2) a nd the muscarinic receptor-gated atrial inwardly rectifying potassium channel, GIRK1. Different beta subunit types interact with these effec tor domains with different efficacies. Furthermore, an N-terminal frag ment of 100 residues interacts with both these effector domains as eff ectively as the whole beta subunit. This domain includes the region wh ere the beta subunit contacts with the alpha subunit in the crystal st ructure and may therefore explain the ability of the alpha subunit to shut off the activity of the beta gamma complex.