spatial relationship between proteins within this macromolecular signaling complex26,92,94,96,101,102 (see Box 2). Interestingly, spectroscopic studies with Gαiβγ heterotrimers have suggested that G protein activation involves a conformational rearrangement of the Gαi and Gβγ subunits, in contrast to the canonical model whereby Gα and Gβγ subunits physically separate103. The ability to undergo rearrangement, however, may be unique to Gαi, since other studies suggest Gαo may dissociate104-107. Together, these studies support a view that GIRK channels reside in a macromolecular signaling complex, governed by protein-protein interactions, limited diffusion and lipid domains2.
