期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2007
卷号：104
期号：6
页码：2001-2006
DOI：10.1073/pnas.0608599104
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 G 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, G{middle dot}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 Gi1 suggests that conformational changes in the {beta}3/2 loop and {beta}6 strand act in concert for efficient nucleotide exchange. Two key residues in the 4 helix were found to define a receptor/Gi coupling specificity determinant.
