Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket.
Journal Article (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
- PMC7313674
Electronic International Standard Serial Number (EISSN)
- 1420-9071
Digital Object Identifier (DOI)
- 10.1007/s00018-018-2996-4
Language
- eng
Conference Location
- Switzerland