Understanding the ternary complex between G protein-coupled receptors (GPCRs), cognate G proteins, and their ligands is an important landmark for drug discovery. Yet, little is known about the specific interactions between GPCRs and G proteins. For a better perspective on the ternary complex dynamics, we adapted a beta(2)-adrenergic receptor(beta(2)AR)-tetGs(alpha) reconstitution system and found evidence that for efficient coupling of the beta(2)AR to Gs does not require specific interactions between the betagamma-subunits and the beta(2)AR. Our results demonstrate that specific interactions between betagamma and the beta(2)AR are not required for G protein activation but likely serve to anchor Gs(alpha) to the plasma membrane. Our results also suggests that the advantages of analysis of G protein activation by using beta(2)AR receptor-tetGs(alpha) system in vitro at the close proximity of the receptor may constitute a simple screening system that avoids false positives and potentially adapted to screen drugs for other GPCRs.