RETRACTED: Structural basis for nucleotide exchange on Gαisubunits and receptor coupling specificity

Abstract
Heterotrimeric G proteins are molecular switches that relay information intracellularly in response to various extracellular signals. How ligand-activated G protein-coupled receptors act at a distance to exert exchange activity on the Gα nucleotide binding pocket is poorly understood. Here we describe the synergistic action of two peptides: one from the third intracellular loop of the D2 dopamine receptor (D2N), and a second, Gα·GDP-binding peptide (KB-752) that mimics the proposed role of Gβγ in receptor-promoted nucleotide exchange. The structure of both peptides in complex with Gαi1suggests that conformational changes in the β3/α2 loop and β6 strand act in concert for efficient nucleotide exchange. Two key residues in the α4 helix were found to define a receptor/Gαicoupling specificity determinant.