RETRACTED: Structural basis for nucleotide exchange on Gαi subunits and receptor coupling specificity (Retracted article. See vol. 109, pg. 1808, 2012)

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 Ga 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 (NN), and a second, Ga-GDP-binding peptide (KB-752) that mimics the proposed role of G beta gamma in receptor-promoted nucleotide exchange. The structure of both peptides in complex with G(alpha i1) suggests that conformational changes in the beta 3/alpha 2 loop and 136 strand act in concert for efficient nucleotide exchange. Two key residues in the alpha 4 helix were found to define a receptor/G(alpha i) coupling specificity determinant.