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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bushdid, C; de March, CA; Topin, J; Do, M; Matsunami, H; Golebiowski, J

Published Date

  • March 2019

Published In

Volume / Issue

  • 76 / 5

Start / End Page

  • 995 - 1004

PubMed ID

  • 30599066

Pubmed Central ID

  • 30599066

Electronic International Standard Serial Number (EISSN)

  • 1420-9071

Digital Object Identifier (DOI)

  • 10.1007/s00018-018-2996-4

Language

  • eng

Conference Location

  • Switzerland