Ligand specificity of odorant receptors
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Odorant receptors belong to class A of the G protein-coupled receptors (GPCRs) and detect a large number of structurally diverse odorant molecules. A recent structural bioinformatic analysis suggests that structural features are conserved across class A of GPCRs in spite of their low sequence identity. Based on this work, we have aligned the sequences of 29 ORs for which ligand binding data are available. Recent site-directed mutagenesis experiments on one such receptor (MOR174-9) provide information that helped to identify nine amino-acid residues involved in ligand binding. Our modeling provides a rationale for amino acids in equivalent positions in most of the odorant receptors considered and helps to identify other amino acids that could be important for ligand binding. Our findings are consistent with most of the previous models and allow predictions for site-directed mutagenesis experiments, which could also validate our model.
KeywordsOlfactory receptors Sequence alignment Odorant binding G protein-coupled receptor Homology modeling
G protein-coupled receptor
We would like to thank Kazushige Touhara and Sayako Katada (University of Tokyo, Japan) for supplying the sequence alignment of bovine rhodopsin and MOR174-9 and the 3D-model structure of the latter, Dr. Alejandro Giorgetti (Università di Roma “La Sapienza”, Italy) for useful discussions and Manuela Schipizza Lough (SISSA/ISAS) for reading the text. This work was supported by INFM-Democritos.
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