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Publication : Two entry tunnels in mouse TAAR9 suggest the possibility of multi-entry tunnels in olfactory receptors.

First Author  Xu Z Year  2022
Journal  Sci Rep Volume  12
Issue  1 Pages  2691
PubMed ID  35177711 Mgi Jnum  J:352583
Mgi Id  MGI:7707638 Doi  10.1038/s41598-022-06591-z
Citation  Xu Z, et al. (2022) Two entry tunnels in mouse TAAR9 suggest the possibility of multi-entry tunnels in olfactory receptors. Sci Rep 12(1):2691
abstractText  Orthosteric binding sites of olfactory receptors have been well understood for ligand-receptor interactions. However, a lack of explanation for subtle differences in ligand profile of olfactory receptors even with similar orthosteric binding sites promotes more exploration into the entry tunnels of the receptors. An important question regarding entry tunnels is the number of entry tunnels, which was previously believed to be one. Here, we used TAAR9 that recognizes important biogenic amines such as cadaverine, spermine, and spermidine as a model for entry tunnel study. We identified two entry tunnels in TAAR9 and described the residues that form the tunnels. In addition, we found two vestibular binding pockets, each located in one tunnel. We further confirmed the function of two tunnels through site-directed mutagenesis. Our study challenged the existing views regarding the number of entry tunnels in the subfamily of olfactory receptors and demonstrated the possible mechanism how the entry tunnels function in odorant recognition.
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