Amino acids involved in conformational dynamics and G protein coupling of an odorant receptor: Targeting gain-of-function mutation

Aya Kato, Sayako Katada, Kazushige Touhara

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Thousands of different odorants are recognized and discriminated by odorant receptors (ORs) in the guanine nucleotide-binding protein (G protein)-coupled seven-transmembrane receptor family. Odorant-bound ORs stimulate Gs-type G proteins, Gαolf, which in turn activates cAMP-mediated signaling pathway in olfactory sensory neurons. To better understand the molecular basis for OR activation and G protein coupling, we analyzed the effects of a series of site-directed mutations of mouse ORs, on function. Mutations of conserved amino acid residues in an intracellular loop or the C-terminus resulted in loss of activity without impairing ligand-binding activity, indicating that these residues are involved in Gαs/olf coupling. Moreover, mutation of the serine in KAFSTC, the OR-specific sequence motif, resulted in a dramatic increase in odorant responsiveness, suggesting that the motif is involved in a conformational change of the receptor that regulates G protein coupling efficiency. Our results provide insights into how ORs switch from an inactive to an active state, as well as where and how activated ORs interact with G proteins.

Original languageEnglish
Pages (from-to)1261-1270
Number of pages10
JournalJournal of Neurochemistry
Volume107
Issue number5
DOIs
Publication statusPublished - Dec 1 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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