Molecular tuning of odorant receptors and its implication for odor signal processing

The discovery of the odorant receptor (OR) family by Buck and Axel in 1991 provided a quantum jump in our understanding of olfactory function. However, the study of the responsiveness of ORs to odor ligands was challenging due to the difficulties in deorphanizing the receptors. In this manuscript, we review recent findings of OR responsiveness that have come about through improved OR deorphanization methods, site-directed mutagenesis, structural modeling studies, and studies of OR responses in situ in olfactory sensory neurons. Although there has been a major leap in our understanding of receptor-ligand interactions and how these contribute to the input to the olfactory system, an improvement of our understanding of receptor structure and dynamics and interactions with intracellular and extracellular proteins is necessary.