Activation of heterotrimeric G-proteins is accomplished exclusively by the action of GPCRs, transmembrane spanning receptors that typically reside in the plasma membrane. G-proteins consist of α, β and γ subunits, each involved in signaling to distinct effectors. The Gβγ dimer binds to a hydrophobic pocket present in Gα-GDP. GTP binding to Gα removes the hydrophobic pocket and reduces the affinity of Gα for Gβγ. Subsequently Gα-GTP dissociates from Gβγ and from the receptor...