G(BETA-GAMMA) DIRECTLY BINDS TO THE CARBOXYL-TERMINUS OF THE G-PROTEIN-GATED MUSCARINIC K+ CHANNEL, GIRK1

beta gamma Subunits of heterotrimeric GTP-binding proteins (G(beta gam ma)) activate the inwardly rectifying muscarinic K+ channel, GIRK1. Th e significant role for the carboxyl (C) terminus of GIRK1 in this inte raction has been suggested. However, it is still unknown whether G(bet a gamma) directly interacts with GIRK1. To elucidate the molecular bas is of G(beta gamma)-activation of GIRK1, we examined the binding prope rties of G(beta gamma) to the C terminus of GIRK1 cloned from mouse br ain cDNA library (MB-GTPK1). The C terminus of MB-GIRK1 fused with glu tathione S-transferase directly bound to purified G(beta gamma). Incub ation of the C terminus with G(i) pretreated with GTP gamma S, but not with GDP, resulted in the binding of G(i beta gamma) to the protein. Purified G(alpha)-GDP, but not G(alpha)-GTP gamma S, inhibited the bin ding of G(beta gamma) to the fusion protein. These results indicate th at G(beta gamma) dissociated from G(alpha) may directly bind to the C terminus of GIRK1. (C) 1995 Academic Press, Inc.