Multiple domains of G protein beta confer subunit specificity in beta gamma interaction.

The expression and assembly of particular combinations of beta and gamma subunit isoforms into beta gamma heterodimers may contribute to the specificity of signal transduction mediated by heterotrimeric guanine nucleotide binding regulatory proteins. Using a transient transfection paradigm to examine selectivity in beta gamma heterodimer formation, we find that gamma 1 interacts with beta 1 but not with beta 2, while both beta subunits interact with gamma 2 and that a beta 2/beta 1 chimera containing the N-terminal 41 residues of beta 2 retained a beta 1 phenotype. These results confirm previous reports and imply that a structure or structures between residues 42 and 340 in the C-terminal region of the beta subunit imparts the ability to distinguish between gamma chains. Extending this chimeric approach to further localize the regions of beta important for selectivity between gamma subunits, we find that the region of beta 1 or beta 2 between residue 215 and the C terminus is sufficient to confer the parental phenotype. Additional mutants implicate multiple regions of beta, including discrete residues in the variable connecting segments joining conserved elements of the fifth and sixth GH-WD repeats toward the C terminus of beta. These findings suggest a multidomain interaction between beta and gamma.