A Short C-Terminal Peptide In G Gamma Regulates G Beta Gamma Signaling Efficacy

G protein beta-gamma (G beta gamma) subunits anchor to the plasma membrane (PM) through the carboxy-terminal (CT) prenyl group in G.. This interaction is crucial for the PM localization and functioning of G beta gamma, allowing GPCR-G protein signaling to proceed. The diverse G. family has 12 members, and we have recently shown that the signaling efficacies of major G beta gamma effectors are G gamma-type dependent. This dependency is due to the distinct series of membrane-interacting abilities of G gamma. However, the molecular process allowing for G beta gamma subunits to exhibit a discrete and diverse range of G gamma-type-dependent membrane affinities is unclear and cannot be explained using only the type of prenylation. The present work explores the unique designs of membrane-interacting CT residues in G gamma as a major source for this G gamma-type-dependent G beta gamma signaling. Despite the type of prenylation, the results show signaling efficacy at the PM, and associated cell behaviors of G beta gamma are governed by crucially located specific amino acids in the five to six residue preprenylation region of G gamma. The provided molecular picture of G gamma-membrane interactions may explain how cells gain G gamma-type-dependent G protein-GPCR signaling as well as how G beta gamma elicits selective signaling at various subcellular compartments.