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 Gαi1 suggests 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/Gαi coupling specificity determinant.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 6 Feb 2007|
- G protein-coupled receptors
- Guanine nucleotide exchange
- Heterotrimeric G proteins