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Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors.

Publication ,  Journal Article
de March, CA; Yu, Y; Ni, MJ; Adipietro, KA; Matsunami, H; Ma, M; Golebiowski, J
Published in: J Am Chem Soc
July 8, 2015

Odorant receptor (OR) genes and proteins represent more than 2% of our genome and 4% of our proteome and constitute the largest subgroup of G protein-coupled receptors (GPCRs). The mechanism underlying OR activation remains poorly understood, as they do not share some of the highly conserved motifs critical for activation of non-olfactory GPCRs. By combining site-directed mutagenesis, heterologous expression, and molecular dynamics simulations that capture the conformational change of constitutively active mutants, we tentatively identified crucial residues for the function of these receptors using the mouse MOR256-3 (Olfr124) as a model. The toggle switch for sensing agonists involves a highly conserved tyrosine residue in helix VI. The ionic lock is located between the "DRY" motif in helix III and a positively charged "R/K" residue in helix VI. This study provides an unprecedented model that captures the main mechanisms of odorant receptor activation.

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Published In

J Am Chem Soc

DOI

EISSN

1520-5126

Publication Date

July 8, 2015

Volume

137

Issue

26

Start / End Page

8611 / 8616

Location

United States

Related Subject Headings

  • Tyrosine
  • Software
  • Sequence Homology, Amino Acid
  • Receptors, Odorant
  • Receptors, G-Protein-Coupled
  • Protein Conformation
  • Protein Binding
  • Mutation
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
 

Citation

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de March, C. A., Yu, Y., Ni, M. J., Adipietro, K. A., Matsunami, H., Ma, M., & Golebiowski, J. (2015). Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors. J Am Chem Soc, 137(26), 8611–8616. https://doi.org/10.1021/jacs.5b04659
March, Claire A. de, Yiqun Yu, Mengjue J. Ni, Kaylin A. Adipietro, Hiroaki Matsunami, Minghong Ma, and Jérôme Golebiowski. “Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors.J Am Chem Soc 137, no. 26 (July 8, 2015): 8611–16. https://doi.org/10.1021/jacs.5b04659.
de March CA, Yu Y, Ni MJ, Adipietro KA, Matsunami H, Ma M, et al. Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors. J Am Chem Soc. 2015 Jul 8;137(26):8611–6.
de March, Claire A., et al. “Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors.J Am Chem Soc, vol. 137, no. 26, July 2015, pp. 8611–16. Pubmed, doi:10.1021/jacs.5b04659.
de March CA, Yu Y, Ni MJ, Adipietro KA, Matsunami H, Ma M, Golebiowski J. Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors. J Am Chem Soc. 2015 Jul 8;137(26):8611–8616.
Journal cover image

Published In

J Am Chem Soc

DOI

EISSN

1520-5126

Publication Date

July 8, 2015

Volume

137

Issue

26

Start / End Page

8611 / 8616

Location

United States

Related Subject Headings

  • Tyrosine
  • Software
  • Sequence Homology, Amino Acid
  • Receptors, Odorant
  • Receptors, G-Protein-Coupled
  • Protein Conformation
  • Protein Binding
  • Mutation
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data