Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity.
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Johnston CA, Siderovski DP
Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity.
Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30.
- PubMed ID
- 17264214 [ View in PubMed]
- 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 Galpha 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, Galpha.GDP-binding peptide (KB-752) that mimics the proposed role of Gbetagamma in receptor-promoted nucleotide exchange. The structure of both peptides in complex with Galpha(i1) suggests that conformational changes in the beta3/alpha2 loop and beta6 strand act in concert for efficient nucleotide exchange. Two key residues in the alpha4 helix were found to define a receptor/Galpha(i) coupling specificity determinant.