Open AccessIdentification of a receptor/G-protein contact site critical for signaling specificity and G-protein activation.
Author(s) -
Jie Liu,
Bruce R. Conklin,
Nathalie Blin,
June Yun,
Jürgen Wess
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.25.11642
Subject(s) - 5 ht5a receptor , g protein , g protein coupled receptor , receptor , g alpha subunit , muscarinic acetylcholine receptor m5 , enzyme linked receptor , biology , transmembrane domain , gtpase activating protein , muscarinic acetylcholine receptor m2 , g protein coupled receptor kinase , microbiology and biotechnology , biochemistry , protein subunit , muscarinic acetylcholine receptor , muscarinic acetylcholine receptor m3 , gene
Each G protein-coupled receptor recognizes only a distinct subset of the many structurally closely related G proteins expressed within a cell. How this selectively is achieved at a molecular level is not well understood, particularly since no specific point-to-point contact sites between a receptor and its cognate G protein(s) have been identified. In this study, we demonstrate that a 4-aa epitope on the m2 muscarinic acetylcholine receptor, a prototypical Gi/o-coupled receptor, can specifically recognize the C-terminal 5 aa of alpha subunits of the Gi/o protein family. The m2 receptor residues involved in this interaction are predicted to be located on one side of an alpha-helical receptor region present at the junction between the third intracellular loop and the sixth transmembrane domain. Coexpression studies with hybrid m2/m3 muscarinic receptors and mutant G-protein alpha q subunits showed that the receptor/G-protein contact site identified in this study is essential for coupling specificity and G-protein activation.