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Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket.

Publication ,  Journal Article
Bushdid, C; de March, CA; Topin, J; Do, M; Matsunami, H; Golebiowski, J
Published in: Cell Mol Life Sci
March 2019

Odorant receptors represent the largest family of mammalian G protein-coupled receptors. Phylogenetically, they are split into two classes (I and II). By analyzing the entire subclass I odorant receptors sequences, we identified two class I-specific and highly conserved motifs. These are predicted to face each other at the extra-cellular portion of the transmembrane domain, forming a vestibular site at the entrance to the orthosteric-binding cavity. Molecular dynamics simulation combined with site-directed mutagenesis and in vitro functional assays confirm the functional role of this vestibular site in ligand-driven activation. Mutations at this part of the receptor differentially affect the receptor response to four agonists. Since this vestibular site is involved in ligand recognition, it could serve ligand design that targets specifically this sub-genome of mammalian odorant receptors.

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Published In

Cell Mol Life Sci

DOI

EISSN

1420-9071

Publication Date

March 2019

Volume

76

Issue

5

Start / End Page

995 / 1004

Location

Switzerland

Related Subject Headings

  • Receptors, Odorant
  • Molecular Dynamics Simulation
  • Models, Molecular
  • Humans
  • Conserved Sequence
  • Biochemistry & Molecular Biology
  • Binding Sites
  • Amino Acid Motifs
  • 3211 Oncology and carcinogenesis
  • 3205 Medical biochemistry and metabolomics
 

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Bushdid, C., de March, C. A., Topin, J., Do, M., Matsunami, H., & Golebiowski, J. (2019). Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket. Cell Mol Life Sci, 76(5), 995–1004. https://doi.org/10.1007/s00018-018-2996-4
Bushdid, Caroline, Claire A. de March, Jérémie Topin, Matthew Do, Hiroaki Matsunami, and Jérôme Golebiowski. “Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket.Cell Mol Life Sci 76, no. 5 (March 2019): 995–1004. https://doi.org/10.1007/s00018-018-2996-4.
Bushdid C, de March CA, Topin J, Do M, Matsunami H, Golebiowski J. Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket. Cell Mol Life Sci. 2019 Mar;76(5):995–1004.
Bushdid, Caroline, et al. “Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket.Cell Mol Life Sci, vol. 76, no. 5, Mar. 2019, pp. 995–1004. Pubmed, doi:10.1007/s00018-018-2996-4.
Bushdid C, de March CA, Topin J, Do M, Matsunami H, Golebiowski J. Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket. Cell Mol Life Sci. 2019 Mar;76(5):995–1004.
Journal cover image

Published In

Cell Mol Life Sci

DOI

EISSN

1420-9071

Publication Date

March 2019

Volume

76

Issue

5

Start / End Page

995 / 1004

Location

Switzerland

Related Subject Headings

  • Receptors, Odorant
  • Molecular Dynamics Simulation
  • Models, Molecular
  • Humans
  • Conserved Sequence
  • Biochemistry & Molecular Biology
  • Binding Sites
  • Amino Acid Motifs
  • 3211 Oncology and carcinogenesis
  • 3205 Medical biochemistry and metabolomics