Until recently, most scientists would have said something like 10,; however, new research suggests a far greater number—perhaps a trillion. The computation begins as signals are received and sorted out in the olfactory bulb, a structure on the underside of the front of the brain. The olfactory bulb also connects directly to the limbic system, the brain area that regulates emotion. A network of connections with other parts of the brain give scents a matchless power to evoke detailed, emotionally charged memories and such complex mental states as nostalgia and longing.
Pheromones are airborne chemicals emitted by individuals that elicit a physiological response in other members of the same species, via the olfactory system. In other animals, pheromones carry messages of alarm and aggression, and they play an essential role in sexual attraction and reproduction. Whether pheromones work similarly in humans is controversial. Some research suggests so: airborne molecules of sex hormones seem to alter hormone secretion in the opposite sex.
For example, the scent of female tears apparently dampens male sexual desire. However, the extent to which pheromones actually influence our actions remains uncertain.
The other primary chemical sense, taste technically, the gustatory system , responds to molecules dissolved in liquid. These molecules enter the system via taste buds: pear-shaped structures in which receptor-bearing cells surround a central pore. There are millions of receptors onsome 10, taste buds.
Most are found in the familiar bumps called papillae that cover the surface of the tongue, but some line the roof of the mouth and the back of the throat. When a molecule of the appropriate taste binds to a receptor, the process changes the electrical charge in the receptor cell, triggering release of a neurotransmitter.
This messenger chemical initiates an electrical impulse in a nearby neuron, which carries the signal to the brain. It used to be thought that receptors for each taste were limited to one section of the tongue the tip of the tongue for sweet, the sides for salt and sour, the back for bitter , but now we know that receptor types are more widely distributed a single taste bud, in fact, may contain receptors for several tastes.
There is no clear organization of taste receptors on the tongue. Taste signals go from the mouth, via cranial nerves, to the medulla oblongata in the brainstem, then up to the thalamus and on to the cortex, where the sensation becomes a perception. In the face of advancement in science and technology, insight into the specifics of the odorant recognition process has not improved significantly. There is no conclusive, concrete evidence as to how odorants bind or dock into a specific OR, which is a shape-sensitive mechanism.
The reason is the notoriously difficult family to which OR belongs to. Despite their importance, limited structural information on GPCRs is available. The standard method of structure prediction by crystallizing the protein X-ray crystallography is not feasible with trans-membrane proteins, as a result, its binding site is experimentally inaccessible.
However, recently, there have been some decent efforts to solve the structure of many GPCRs with X-ray diffraction or other techniques. Nevertheless, it is difficult to figure out the structural changes OR undergo at the molecular level. The atomic-level structure has been solved for bovine rhodopsin [ , ] and beta-adrenergic receptor [ , , ] by x-ray diffraction studies. Considering the importance, diversity and the vital role of GPCRs, it is important to develop theoretical methods to predict their structure and function [ , ].
Nagarajan et al developed computational strategies and techniques to predict the structure of GPCRs MembStruck protocol and ligand binding sites HierDock protocol , which were validated by comparing the predicted models to the experimental data of rhodopsin and bacteriorhodopsin [ ]. MembStruck protocol for GPCR structure prediction begins with a prediction of trans-membrane region using hydropathicity analysis [ ] in combination with input from multi-sequence profiles.
They are optimized with fixed bonds and angles. Once the TM scaffold is built, the axis of each helix in seven-helical TM bundle is rotated for hydrophobic-based positioning so that the net hydrophobic moment of each helix points outward, towards the membrane. The loops and termini are added, followed by coarse-grain optimization while simulating the surrounding lipid bi-layer using lipid molecules [ ]. HierDock protocol [ ] has been applied successfully to predict ligand binding sites of both globular and membrane proteins [ , ].
Since the ligand binding site of GPCRs is not known beforehand, therefore coarse grain docking technique is applied for scanning entire protein to identify probable sites.
Often used in conjunction with Membstruck protocol, it involves the progression of steps which discards ligand configurations failing to meet the criteria established while coarse grain docking. For each site, relative energies of ligands are determined as a difference between potential energy of ligand in the solvent and ligand in the protein. Low energy structures are further refined. The final protein-ligand complex could be used to explore binding mechanisms.
Anselmi et al. Moreover, they proposed a correlation with the odorous properties of the ligands and investigated the residues involved in the binding. The study also highlights the olfactive stimulation of the OR with odorous molecules using calcium imaging or electrophysiological recordings [ ].
The results of potentially challenging and complicated modeling strategies are required to be stored and disseminated, so that they can be used for better understanding. It provides insights into the structure, function, and evolution of ORs. It contains OR orthologs from six mammalian species, namely, mouse, rat, chimpanzee, cow, dog, platypus, and opossum.
The information is stored using an automated computational pipeline, which mines the relevant genes out of complete genome [ ]. The information involves genomic organization of ORs into clusters, identification of clusters, gene models, Microarray and ESTs data. ORDB contains genomics and proteomics information related to ORs and other chemosensory receptors [ 49 ]. Proposed nomenclature for ORDB includes receptor superfamily i.
For example, OR1M1, where OR represents olfactory superfamily, 1 is for the family, M for subfamily, 1 represents gene number within the subfamily.
OdorDB provides information about the functional aspect of ORs i. At present, it stores information of approximately odorants, for 75 odorants, their interacting ORs experimental studies is known. ORModelDB stores computationally predicted structures of.
ORs based on ab initio or semi-empirical methods with the aim to decipher the OR-odorant interaction mechanism at a molecular level. The number of models is less 08 models indicating gaps in in-silico aspect of OR-odorant interaction. All four databases are cross-linked. It stores Affymetrix gene-chip data in the olfactory epithelium as well as other tissues of rodents in minimum information about a microarray experiment MIAME format.
ORMD contains both private as well as public gene expression data. It allows users to not only deposit gene expression data, but also manage their experiments.
ORs for a query chemical compound are predicted based on two functions, namely, odorant verification and OR identification. It houses manually curated information from literature about odorants and ORs in both humans as well as mouse.
It is an effective platform for identifying probable ORs, odorants, Odorant-OR interaction and for basic olfaction research [ ]. OlfactionDB is another free, manually curated, comprehensive, and publicly available database storing information of approximately odorant-receptor interactions.
It is developed for managing information about odorants and their receptors. Olfaction is the oldest sensory modality known in evolution. Odor detection is accomplished by an array of different ORs expressed by olfactory sensory neurons in the nasal olfactory epithelium.
Olfaction signal transduction is crucial for sensing our environment. There are unanswered questions, however. Now, we have some data; the advancement in biological techniques has accelerated research in olfaction. With the knowledge of ORs, as multifunctional signaling molecules, their belongingness to GPCR family, OBPs working as a pre-selection filter, various experimental evidences of OR-odorant interactions, a lot of efforts have been made to get insights into structural and functional aspects of ORs.
GPCR research is confined due to the limited availability of experimentally derived structures, which is a challenging task both experimentally and computationally. The mechanism underlying the expression of even a single allele in any given OSN is not yet understood.
Studies to identify conserved motifs in the transcription factor binding site or promoter site, residue motifs specific to binding site have failed time and again thereby marking a new area of research. ORs structural and functional diversity is consistent with their ability to recognize structurally diverse chemical compounds. Odors are encrypted using a combinatorial approach i.
Also, the perception quality of odorant varies with concentration. Diverse approaches have yielded largely convergent results. Mechanistics of odorant-OR interactions, ORs activation and desensitization are still a black box. It is also not known as to how different areas of the olfactory cortex receive signals; from different subsets of ORs or from all the ORs.
Further, how are the signals organized in the cortex? There are several such queries which require more experimentation and in-depth research in olfaction.
Computational analysis structure modeling, docking and simulation protocols offers a view of the OR-odorant interactions for a better understanding of what leads to olfaction.
By modeling ORs, one can predict the underlying structural and functional relationship of odorous compounds coupling to their corresponding receptors.
In the absence of experimental studies, site-directed mutagenesis could be used in modeling and docking studies to decipher the 3D structure of ORs. Computational databases storing complete human OR universe known till date are a fundamental asset for future research in olfaction. Twenty-seven years after the discovery of ORs, there is still much more to research and learn about their structure, function and mechanism. The authors declare no conflict of interest, financial or otherwise.
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This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4. This article has been cited by other articles in PMC. Abstract Olfaction, the sense of smell detects and discriminate odors as well as social cues which influence our innate re-sponses.
Keywords: GPCR, olfactory bulb, odor, receptor, signal transduction. Among all species, the olfactory system has evolved in response to the two problems; to detect and discriminate between the array of chemical compounds and to the unique sensory challenges faced by them. Open in a separate window.
Table 1 Human olfactory receptor family. Structural Features of Olfactory Receptors ORs belong to the GPCRs-rhodopsin family, which plays a key role in cell recognition, activating signal transduction, mediating senses smell, taste, pain, sight [ 7 , 44 , 70 , 77 , 78 ]. Trace amine-associate Receptors TAARs Discovered in , TAARs, distantly related to biogenic amine GPCRs [ , ], recognize low abundance neurotransmitters trace amines [ ] via a key salt bridge involving a conserved trans-membrane three aspartic acid [ ] and evoke stereotyped behaviors [ ].
The Steric Theory of Odor The most sophisticated theory for olfaction given by Troland is based on the steric factors. The Radiation Theory Every atom or molecule has associated electron vibrations which set up the vibrations in the surrounding medium, and are reinforced by resonance. The Vibrational Theories of Odor Infra-red Theories The theory associates odor with infrared resonance IR , measurements of molecule vibration [ , ].
Ultraviolet Theory Given by Heyninx [ ], the theory states that ultraviolet absorption bands of odorous molecules are due to the constituent molecules which vibrate with a frequency equivalent to that of the absorbed light.
Raman Shift Theory When a substance is radiated by laser light of particular wavelength, the energy of laser photons is shifted either up or down due to which substance emits shorter or longer wavelengths than the original light. Vibrational Induced Electron Tunneling Spectroscopy Theory The electron tunneling involves the transfer of electrons down the backbone of the protein. Mechanical Theories It states that the air movement in nose leads to vibration of olfactory hairs and the vibrations were modulated by odorants according to their molecular weight and momentum.
Stimulus Pattern Theories An extensive work was carried out by Adrian in the electrophysiology of olfaction [ ]. Phase Boundary Theories These theories deal with the mechanism of receptor stimulation. Enzyme Theories The modern theories of olfactory stimulation revolve around the presence of various active enzymes in olfactory epithelium which are selectively inhibited by odorants. Click here to view.
Harel D. Towards an odor communication system. Breer H. Olfactory receptors: molecular basis for recognition and discrimination of odors. Spehr M. Olfactory receptors: G protein-coupled receptors and beyond. Touhara K. Sensing odorants and pheromones with chemosensory receptors. Sarafoleanu C. The importance of the olfactory sense in the human behavior and evolution. Bear D. Evolution of the genetic and neural architecture for vertebrate odor perception.
Buck L. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Zhang X. The olfactory receptor gene superfamily of the mouse. Lander E. Initial sequencing and analysis of the human genome. Venter J. The sequence of the human genome.
Glusman G. The complete human olfactory subgenome. Genome Res. Niimura Y. Comparative evolutionary analysis of olfactory receptor gene clusters between humans and mice. Zozulya S. The human olfactory receptor repertoire. Genome Biol. Malnic B. The human olfactory receptor gene family. Godfrey P. The mouse olfactory receptor gene family. The sense of smell: multiple olfactory subsystems. Life Sci. Strotmann J. Olfactory receptor proteins in axonal processes of chemosensory neurons.
Menco B. Ultrastructural localization of olfactory transduction components: the G protein subunit Golf alpha and type III adenylyl cyclase. Mombaerts P. How smell develops. Lodovichi C. Odorant receptors in the formation of the olfactory bulb circuitry. Physiology Bethesda ; 27 4 — Witt M. Structure and function of the vomeronasal organ. Meredith M. Human vomeronasal organ function: a critical review of best and worst cases.
Dulac C. A novel family of genes encoding putative pheromone receptors in mammals. Rodriguez I. Novel human vomeronasal receptor-like genes reveal species-specific families.
Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system. Roppolo D. Gene cluster lock after pheromone receptor gene choice. EMBO J. Odorant receptor gene choice in olfactory sensory neurons: the one receptor-one neuron hypothesis revisited. Genetic analysis of brain circuits underlying pheromone signaling. Shi P. Comparative genomic analysis identifies an evolutionary shift of vomeronasal receptor gene repertoires in the vertebrate transition from water to land.
Grus W. Dramatic variation of the vomeronasal pheromone receptor gene repertoire among five orders of placental and marsupial mammals. Herrada G. A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Matsunami H.
A multigene family encoding a diverse array of putative pheromone receptors in mammals. Ryba N. A new multigene family of putative pheromone receptors. Young J. V2R gene families degenerated in primates, dog and cow, but expanded in opossum. Trends Genet. Silvotti L. Combinatorial co-expression of pheromone receptors, V2Rs. A putative pheromone receptor gene expressed in human olfactory mucosa. Savic I.
Smelling of odorous sex hormone-like compounds causes sex-differentiated hypothalamic activations in humans. Kosaka T. Olfactory Anatomy. Seven-transmembrane proteins as odorant and chemosensory receptors. Molecular biology of odorant receptors in vertebrates. Pilpel Y. Molecular biology of olfactory receptors. Essays Biochem. Rouquier S. Distribution of olfactory receptor genes in the human genome. The olfactory receptor gene repertoire in primates and mouse: evidence for reduction of the functional fraction in primates.
Serizawa S. Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse. Lewcock J. Humans have about 12 million olfactory receptors distributed among hundreds of different receptor types that respond to different odors. Twelve million seems like a large number of receptors, but compare that to other animals: rabbits have about million, most dogs have about 1 billion, and bloodhounds dogs selectively bred for their sense of smell have about 4 billion. Human olfactory system : In the human olfactory system, a bipolar olfactory neurons extend from b the olfactory epithelium, where olfactory receptors are located, to the olfactory bulb.
Olfactory neurons are bipolar neurons neurons with two processes from the cell body. Each neuron has a single dendrite buried in the olfactory epithelium; extending from this dendrite are 5 to 20 receptor-laden, hair-like cilia that trap odorant molecules. The sensory receptors on the cilia are proteins. It is the variations in their amino acid chains that make the receptors sensitive to different odorants. Each olfactory sensory neuron has only one type of receptor on its cilia. The receptors are specialized to detect specific odorants, so the bipolar neurons themselves are specialized.
When an odorant binds with a receptor that recognizes it, the sensory neuron associated with the receptor is stimulated. Olfactory stimulation is the only sensory information that directly reaches the cerebral cortex, whereas other sensations are relayed through the thalamus.
Detecting a taste gustation is fairly similar to detecting an odor olfaction , given that both taste and smell rely on chemical receptors being stimulated by certain molecules. The primary organ of taste is the taste bud. A taste bud is a cluster of gustatory receptors taste cells that are located within the bumps on the tongue called papillae singular: papilla.
There are several structurally-distinct papillae. Filiform papillae, which are located across the tongue, are tactile, providing friction that helps the tongue move substances; they contain no taste cells. In contrast, fungiform papillae, which are located mainly on the anterior two-thirds of the tongue, each contain one to eight taste buds; they also have receptors for pressure and temperature. The large circumvallate papillae contain up to taste buds and form a V near the posterior margin of the tongue.
Taste buds : a Foliate, circumvallate, and fungiform papillae are located on different regions of the tongue. In humans, there are five primary tastes; each taste has only one corresponding type of receptor. If that is impossible, pay particular attention to the dates stamped on most perishable foods and do not consume them after that date.
UConn Health. Search University of Connecticut. A to Z Index. If you wish to be evaluated here, call What Are the Chemical Senses? Anosmia - total loss of smell Hyposmia - partial loss of smell Parosmia - perceiving a smell when no odor is present or perceiving familiar odors as smelling strange Hypogeusia - a diminished sense of taste Dysgeusia - a persistent taste, usually unpleasant What Are the Causes of Taste and Smell Disorders?
Are Taste and Smell Related?
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