The sense of smell: molecular basis of odorant recognition

Abstract

Most animal species rely on odorant compounds to locate food, predators, or toxins. The sense of smell is also involved in animal communication, and revealing the underlying mechanisms will therefore facilitate a deeper understanding of animal behaviour. Since the 1940s different theories have speculated on the fundamental basis of olfaction. It was assumed that odorant molecules were recognized by selective protein receptors in the nose, triggering a nervous signal processed by the brain. The discovery of these receptors in the early 1990s allowed great progress in understanding the physiological and biochemical principles of olfaction. An overview of the different mechanisms involved in the coding of odour character as well as odour intensity is presented here, focusing on the biochemical basis of odorant recognition. Despite the enormous progress achieved in recent years, details of odorant-receptor interaction at the molecular level and the mechanisms of olfactory receptor activation are poorly understood. The likely role of metal ions in odorant recognition is discussed, and also the perireceptor events involved in odorant transport and biotransformation, with a view to providing a comprehensive overview of mammalian olfaction to guide future computational structural models and the design of functional experiments. Recent studies have analysed the olfactory genome of several species, providing information about the evolution of olfaction. The role of the olfactory system in animal communication is also described.

Honeybees (Apis mellifera) learn to discriminate the smell of organic compounds from their respective deuterated isotopomers

“…Insights about the potential mechanisms underlying the interaction and specificity of odorant receptors come from recent advances in our understanding of the interactions of G protein-coupled receptors with their ligands [14], which include hormone and neurotransmitter receptors as well as photoreceptors, taste receptors and ORs. However, the location of the agonist binding sites in these receptors is highly variable [15], and three-dimensional structures and potential binding sites are known only for a few ORs [16], which hampers computational models for determining potential olfactory ligands and specific structural motifs (often referred to as 'odotopes') within odorant molecules [17]. Early ideas suggested a key/lock type mechanism between the odorant and the OR protein [18,19], and much research has been performed during the past 50 years to describe the interactions of these odotopes with particular sites of the OR molecules.…”

Molecular recognition in olfaction

“…One attempt to find a way forward was to suggest that receptors only bind to parts of the odourant: this is the odotope theory [112]. The positive side of this theory is that odour appears to be a characteristic of chemical groups [111] (for example -SH or -NH 2 groups have odours associated with them), and thus the receptors could bind these groups. It is not clear how this operates in practice though [52].…”

“…Even if just one component of the ligand is key to the stability (e.g. some group that binds strongly to a metal ion [111]), the rearrangement could be sensitive to the remainder of the molecule.…”

“…We stress again that the vibrational theory considered here is sensitive to odourant structure as the odourant must reside in the receptor for its vibrational spectrum to be analyzed. The presence of zinc in the receptor may help bind odourants [111], but the limitations of a purely structural approach [40] can be overcome by the additional information acquired from the vibrational spectrum. Similarly, the limitations of a pure vibrational theory, such as being unable to distinguish enantiomers [50], are removed by the structural restraints imposed by the need for residency [118].…”

Genomics of selected human odorant receptors

“…Moreover, human sensual pleasure (e.g., the odor of perfume) is one important aspect of life quality. So this primal sense can be designated as a major agent for communication between the individual and its environment [2].…”