Structural basis for nucleotide exchange on Gαi subunits and receptor coupling specificity

Christopher A. Johnston, David P. Siderovski

Research output: Contribution to journalArticle

34 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)2001-2006
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number6
DOIs
StatePublished - 6 Feb 2007

Keywords

  • G protein-coupled receptors
  • Guanine nucleotide exchange
  • Heterotrimeric G proteins

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