QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 10, 2004, 24(45):10128-10137; doi:10.1523/JNEUROSCI.3117-04.2004

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (28) Citing Articles via Google Scholar Google Scholar Articles by Luu, P. Articles by Ngai, J. Search for Related Content PubMed PubMed Citation Articles by Luu, P. Articles by Ngai, J.

 Previous Article  |  Next Article 

Cellular/Molecular
Molecular Determinants of Ligand Selectivity in a Vertebrate Odorant Receptor

Percy Luu,¹ Francine Acher,² Hugues-Olivier Bertrand,³ Jinhong Fan,¹ and John Ngai¹

¹Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, ²Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Unité Mixte de Recherche 8601, Centre National de la Recherche Scientifique, Université René Descartes-Paris V, 75270 Paris Cedex 06, France, and ³Accelrys, 91893 Orsay Cedex, France

The identification of the chemical structure of an odorant by the vertebrate olfactory system is thought to occur through the combinatorial activity from multiple receptors, each tuned to recognize different chemical features. What are the molecular determinants underlying the selectivity of individual odorant receptors for their cognate ligands? To address this question, we performed molecular modeling and site-directed mutagenesis on the ligand-binding region of two orthologous amino acid odorant receptors belonging to the "C family" of G-protein-coupled receptors in goldfish and zebrafish. We identified the critical ligand-receptor interactions that afford ligand binding as well as selectivity for different amino acids. Moreover, predictions regarding binding pocket structure allowed us to alter, in a predictable manner, the receptor preferences for different ligands. These results reveal how this class of odorant receptor has evolved to accommodate ligands of varying chemical structure and further illuminate the molecular principles underlying ligand recognition and selectivity in this family of chemosensory receptors.

Key words: olfaction; olfactory; odorant receptor; G-protein-coupled receptor; ligand binding; signal transduction

---

Received July 30, 2004; revised September 30, 2004; accepted October 1, 2004.

This article has been cited by other articles:

				T. Koide, N. Miyasaka, K. Morimoto, K. Asakawa, A. Urasaki, K. Kawakami, and Y. Yoshihara Olfactory neural circuitry for attraction to amino acids revealed by transposon-mediated gene trap approach in zebrafish PNAS, June 16, 2009; 106(24): 9884 - 9889. [Abstract] [Full Text] [PDF]

				K. A. Johnstone, K. L. Ciborowski, K. P. Lubieniecki, W. Chow, R. B. Phillips, B. F. Koop, W. C. Jordan, and W. S. Davidson Genomic Organization and Evolution of the Vomeronasal Type 2 Receptor-Like (OlfC) Gene Clusters in Atlantic Salmon, Salmo salar Mol. Biol. Evol., May 1, 2009; 26(5): 1117 - 1125. [Abstract] [Full Text] [PDF]

				A. A. Nikonov and J. Caprio Highly Specific Olfactory Receptor Neurons for Types of Amino Acids in the Channel Catfish J Neurophysiol, October 1, 2007; 98(4): 1909 - 1918. [Abstract] [Full Text] [PDF]

				R. P. Ferrer and R. K. Zimmer Chemosensory reception, behavioral expression, and ecological interactions at multiple trophic levels J. Exp. Biol., May 15, 2007; 210(10): 1776 - 1785. [Abstract] [Full Text] [PDF]

				D. Kuang, Y. Yao, D. MacLean, M. Wang, D. R. Hampson, and B. S. W. Chang From the Cover: Ancestral reconstruction of the ligand-binding pocket of Family C G protein-coupled receptors PNAS, September 19, 2006; 103(38): 14050 - 14055. [Abstract] [Full Text] [PDF]

				Y. Nie, J. R. Hobbs, S. Vigues, W. J. Olson, G. L. Conn, and S. D. Munger Expression and Purification of Functional Ligand-Binding Domains of T1R3 Taste Receptors Chem Senses, July 1, 2006; 31(6): 505 - 513. [Abstract] [Full Text] [PDF]

				M. Wang, Y. Yao, D. Kuang, and D. R. Hampson Activation of Family C G-protein-coupled Receptors by the Tripeptide Glutathione J. Biol. Chem., March 31, 2006; 281(13): 8864 - 8870. [Abstract] [Full Text] [PDF]

				P. C. Lai, M. S. Singer, and C. J. Crasto Structural Activation Pathways from Dynamic Olfactory Receptor-Odorant Interactions Chem Senses, November 1, 2005; 30(9): 781 - 792. [Abstract] [Full Text] [PDF]

				Y. Sato, N. Miyasaka, and Y. Yoshihara Mutually Exclusive Glomerular Innervation by Two Distinct Types of Olfactory Sensory Neurons Revealed in Transgenic Zebrafish J. Neurosci., May 18, 2005; 25(20): 4889 - 4897. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help