|ZFIN ID: ZDB-PUB-041115-2|
Molecular determinants of ligand selectivity in a vertebrate odorant receptor
Luu, P., Acher, F., Bertrand, H.O., Fan, J., and Ngai, J.
|Source:||The Journal of neuroscience : the official journal of the Society for Neuroscience 24(45): 10128-10137 (Journal)|
|Registered Authors:||Ngai, John|
|Keywords:||olfaction; olfactory; odorant receptor; G-protein-coupled receptor; ligand binding; signal transduction|
|PubMed:||15537883 Full text @ J. Neurosci.|
Luu, P., Acher, F., Bertrand, H.O., Fan, J., and Ngai, J. (2004) Molecular determinants of ligand selectivity in a vertebrate odorant receptor. The Journal of neuroscience : the official journal of the Society for Neuroscience. 24(45):10128-10137.
ABSTRACTThe 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.
- Genes / Markers (1)