Cloning, functional expression and characterization of a human olfactory receptor

The human olfactory system can recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants begins with the binding of an odorant ligand to a specific receptor protei n on the olfactory neuron cell surface, To address the problem of olfactory perception at a molecular level, we have cloned, functionally expressed an d characterized the first human olfactory receptor (OR 17-40). Application of a mixture of hundred different odorants elicited a transient increase in intracellular calcium at HEK 293-cells which were transfected with a plasm id containing the receptor encoding DNA and a membrane import sequence, By subdividing the odorant mixture in smaller groups we could identify a singl e component which represented the only effective substance: helional, Testi ng some structurally closely related molecules we found only one other comp ound which also could activate the receptor: heliotropyl acetone, Ail other compounds tested were completely ineffective. These findings represent the beginning of molecular understanding of odorant recognition in humans.