Receptor-G protein coupling is established by a potential conformational switch in the βγ complex

Receptor-G protein interaction is characterized by cycles of association and dissociation. We present evidence which indicates that during receptor-G protein interaction, the C-terminal tail of the G protein γ subunit, which is masked in the βγ complex, is exposed and establishes high-affinity contact with the receptor. This potential conformational switch provides a mechanism to regulate receptor-G protein coupling. This switch may also be significant for the role of the βγ complex in regulation of effector function.