A single olfactory receptor specifically binds a set of odorant molecules.
The sense of smell is mediated by the initiation of action potential in olfactory sensory neurons during odor stimulation. However, little is known about odorant-olfactory receptor (OR) recognition mechanisms. In the present work, we identified the structural motifs of odorant molecules required to activate mouse OR912-93 by detection of the odorant response using calcium measurement in cells transfected with OR and G(alpha)q and G(alpha)15 proteins. The use of sets of odorants led to the identification of ketones with an aliphatic carbon chain length >or= four carbon atoms and a carbonyl group preferentially located in position C2 or C3. The threshold of detection of these odorants is as low as 10(-6)-10(-8)m. No other odorant ligand, out of 70 representatives of the odorant world, was active. The human ortholog of OR912-93 is not functional, suggesting that apart from a stop-mutation located at the 5'-end that was corrected in the construct, it incurred other deleterious mutations during evolution.
Gaillard
Isabelle
I
IGH, CNRS UPR 1142, rue de la Cardonille, 34396 Montpellier cedex 5, France. gaillard@igh.cnrs.fr
Rouquier
Sylvie
S
Pin
Jean-Philippe
JP
Mollard
Patrice
P
Richard
Sylvain
S
Barnabé
Cécile
C
Demaille
Jacques
J
Giorgi
Dominique
D
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D009812:Odorants / Q000032:analysis*; D018034:Olfactory Receptor Neurons / Q000187:drug effects* / Q000378:metabolism; D018035:Receptors, Odorant / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012903:Smell / Q000502:physiology*
D007659:Ketones; D018035:Receptors, Odorant; D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins