Inactive-state preassembly of Gq-coupled receptors and G q heterotrimers

Kou Qin, Chunmin Dong, Guangyu Wu, Nevin A. Lambert

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

G protein-coupled receptors (GPCRs) transmit signals by forming active-state complexes with heterotrimeric G proteins. It has been suggested that some GPCRs also assemble with G proteins before ligand-induced activation and that inactive-state preassembly facilitates rapid and specific G protein activation. However, no mechanism of preassembly has been described, and no functional consequences of preassembly have been demonstrated. Here we show that M3 muscarinic acetylcholine receptors (M3R) form inactive-state complexes with Gq heterotrimers in intact cells. The M3R C terminus is sufficient, and a six-amino-acid polybasic sequence distal to helix 8 ( 565KKKRRK570) is necessary for preassembly with G q. Replacing this sequence with six alanine residues prevents preassembly, slows the rate of Gq activation and decreases steady-state agonist sensitivity. That other Gq-coupled receptors possess similar polybasic regions and also preassemble with Gq suggests that these GPCRs may use a common preassembly mechanism to facilitate activation of Gq heterotrimers.

Original languageEnglish (US)
Pages (from-to)740-747
Number of pages8
JournalNature Chemical Biology
Volume7
Issue number10
DOIs
StatePublished - Oct 2011

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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