{"version":1,"updated":"2026-10-08","license":"https://www.radlerparfums.com/terms","label":"educational model, not a measured binding","about":"The receptor model’s nine steps, compiled from data/labs/receptor.json and the records: each step’s words, what its drawing adds that is only illustrative, and the evidence for its facts (quotes of Source records, checked against the filed texts at build time, or records of this site).","molecule":{"id":"vanillin","name":"vanillin","formula":"C8H8O3","smiles":"COC1=C(C=CC(=C1)C=O)O","pubchem_cid":1183,"url":"https://www.radlerparfums.com/molecule/vanillin"},"accord":{"id":"amber-teaching-accord","name":"An amber","url":"https://www.radlerparfums.com/accord/amber-teaching-accord","disclaimer":"A teaching accord for learning: not a Radler formula, not a finished perfume, not safety-assessed; do not make it for skin.","components":[{"type":"Material","id":"labdanum-absolute","name":"labdanum absolute","parts":45},{"type":"Molecule","id":"vanillin","name":"vanillin","parts":35},{"type":"Material","id":"frankincense-resin","name":"frankincense","parts":20}]},"steps":[{"n":1,"id":"perfume","title":"The perfume","text":"On a paper strip, a drop of the house’s amber teaching accord: labdanum absolute (45 parts), vanillin (35 parts), frankincense (20 parts). As the drop evaporates, molecules of each component leave the paper. The model follows one of them: vanillin, C8H8O3.","drawn":"The strip and the molecules rising from it are drawn for the idea; how many leave, and how fast, is not modeled.","evidence":[{"record":"accord/amber-teaching-accord","name":"amber teaching accord","href":"/accord/amber-teaching-accord","field":null,"value":null},{"record":"molecule/vanillin","name":"vanillin","href":"/molecule/vanillin","field":"formula","value":"C8H8O3"}]},{"n":2,"id":"nose","title":"Into the nose","text":"Breathed in, the molecule reaches the olfactory epithelium high in the nose and dissolves in the mucus that covers it. Under the mucus are the fine cilia of olfactory sensory neurons, and in the membrane of each cilium sit the odorant receptors.","drawn":"The membrane is drawn as two rows of lipid heads; the path the molecule takes is illustrative.","evidence":[{"source":"OLF-4","citation":"Genovese F, Reisert J, Kefalov VJ. Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics. Frontiers in Cellular Neuroscience 2021;15:761416. DOI 10.3389/fncel.2021.761416. PMCID PMC8531253.","url":"https://doi.org/10.3389/fncel.2021.761416","quotes":[{"text":"the ligands are dissolved in the mucus covering the surface of the olfactory epithelium and come into direct contact with the OR proteins expressed in the OSN ciliary membrane","where":"reports/l2/fulltext/OLF-4.txt:30","row":false}]}]},{"n":3,"id":"receptor","title":"A receptor","text":"An odorant receptor is a protein that crosses the cell membrane seven times: seven helices, joined by three loops outside the cell and three inside. It belongs to the large family of G protein-coupled receptors. Linda Buck and Richard Axel described the gene family of these receptors in the rat in 1991; the human genome carries about 400 of them.","drawn":"The receptor drawn is no particular receptor. Its seven helices stand side by side, as if the bundle were unrolled; in the cell they form a ring.","evidence":[{"source":"OLF-5","citation":"Wang J, Zhang Q, Fan W, Shi Q, Mao J, Xie J, Chai G, Zhang C. Deciphering olfactory receptor binding mechanisms: a structural and dynamic perspective on olfactory receptors. Frontiers in Molecular Biosciences 2025;11:1498796. DOI 10.3389/fmolb.2024.1498796. PMCID PMC11751049.","url":"https://doi.org/10.3389/fmolb.2024.1498796","quotes":[{"text":"A common feature of these receptors is that they all possess seven transmembrane α-helices in their three-dimensional structure","where":"reports/l2/fulltext/OLF-5.txt:297","row":false},{"text":"In addition to these transmembrane regions, olfactory receptors feature three extracellular loops (ECLs) and three intracellular loops (ICLs)","where":"reports/l2/fulltext/OLF-5.txt:315","row":false},{"text":"discovering a large gene family comprising approximately 1,000 distinct genes, which give rise to a corresponding number of olfactory receptor types","where":"reports/l2/fulltext/OLF-5.txt:13","row":false}]},{"source":"OLF-4","citation":"Genovese F, Reisert J, Kefalov VJ. Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics. Frontiers in Cellular Neuroscience 2021;15:761416. DOI 10.3389/fncel.2021.761416. PMCID PMC8531253.","url":"https://doi.org/10.3389/fncel.2021.761416","quotes":[{"text":"In both photoreceptors and OSNs, the detection of stimuli is mediated by G protein-coupled receptors.","where":"reports/l2/fulltext/OLF-4.txt:29","row":false}]},{"source":"TXT-BUCK-AXEL-1991","citation":"Linda Buck and Richard Axel. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65 (1991) 175–187. Publisher (Elsevier BV), DOI 10.1016/0092-8674(91)90418-X (checked 2026-10-08).","url":"https://doi.org/10.1016/0092-8674(91)90418-X","quotes":[]},{"source":"OLF-6","citation":"Billesbølle CB, de March CA, van der Velden WJC, Ma N, Tewari J, del Torrent CL, Li L, Faust B, Vaidehi N, Matsunami H, Manglik A. Structural basis of odorant recognition by a human odorant receptor. Nature 2023;615(7953):742–749. DOI 10.1038/s41586-023-05798-y. PMID 36922591. PMCID PMC10580732 (author manuscript).","url":"https://europepmc.org/articles/PMC10580732","quotes":[{"text":"This task is accomplished by the combinatorial activation of approximately 400 odorant G protein-coupled receptors encoded in the human genome.","where":"docs/sources/OLF-6-billesbolle-2023-or51e2-structure.md:14","row":false}]}]},{"n":4,"id":"binding","title":"Binding","text":"The molecule settles into a pocket among the helices. It is held by weak contacts, not a lasting chemical bond, and for a matter of milliseconds before it lets go. In the structure of one human receptor, OR51E2, its odorant (propionate) sits in a small enclosed pocket.","drawn":"No receptor for vanillin is drawn here: the pocket, the fit and the angle are illustrative. Most odorant receptors have no known odorant yet; a 2025 review’s table of receptors with reported odorants lists vanillin for five of them (OR1L3, OR2G2, OR2M4, OR2T10 and OR2T34), all from one 2015 study.","evidence":[{"source":"OLF-4","citation":"Genovese F, Reisert J, Kefalov VJ. Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics. Frontiers in Cellular Neuroscience 2021;15:761416. DOI 10.3389/fncel.2021.761416. PMCID PMC8531253.","url":"https://doi.org/10.3389/fncel.2021.761416","quotes":[{"text":"The binding of the ligand to the receptor protein is noncovalent and rapidly reversible.","where":"reports/l2/fulltext/OLF-4.txt:30","row":false},{"text":"the dwell time of the odorant ligand on the OR appears to be very short and on a millisecond timescale","where":"reports/l2/fulltext/OLF-4.txt:43","row":false}]},{"source":"OLF-6","citation":"Billesbølle CB, de March CA, van der Velden WJC, Ma N, Tewari J, del Torrent CL, Li L, Faust B, Vaidehi N, Matsunami H, Manglik A. Structural basis of odorant recognition by a human odorant receptor. Nature 2023;615(7953):742–749. DOI 10.1038/s41586-023-05798-y. PMID 36922591. PMCID PMC10580732 (author manuscript).","url":"https://europepmc.org/articles/PMC10580732","quotes":[{"text":"Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation.","where":"docs/sources/OLF-6-billesbolle-2023-or51e2-structure.md:18","row":false}]},{"source":"OLF-5","citation":"Wang J, Zhang Q, Fan W, Shi Q, Mao J, Xie J, Chai G, Zhang C. Deciphering olfactory receptor binding mechanisms: a structural and dynamic perspective on olfactory receptors. Frontiers in Molecular Biosciences 2025;11:1498796. DOI 10.3389/fmolb.2024.1498796. PMCID PMC11751049.","url":"https://doi.org/10.3389/fmolb.2024.1498796","quotes":[{"text":"the current landscape reveals that more than 80% of olfactory receptors remain enigmatic orphan receptors while their ligands shrouded in mystery","where":"reports/l2/fulltext/OLF-5.txt:276","row":false},{"text":"Deorphanized olfactory receptor (ORs) with corresponding ligand.","where":"reports/l2/fulltext/OLF-5.txt:17","row":false},{"text":"OR1L3\nvanillinα-damascone\nGonzalez-Kristeller et al. (2015)","where":"reports/l2/fulltext/OLF-5.txt:39","row":true},{"text":"OR2G2\nmaltyl isobutyratecinnamaldehydevanillinα-damascone\nGonzalez-Kristeller et al. (2015)","where":"reports/l2/fulltext/OLF-5.txt:72","row":true},{"text":"OR2M4\nfructonecinnamaldehydevanillinnerolidolα-damascone estragolecresyl methyl ether\nGonzalez-Kristeller et al. (2015)","where":"reports/l2/fulltext/OLF-5.txt:90","row":true},{"text":"OR2T10\nmaltyl isobutyrateterpinyl acetate; cinnamaldehydevanillinα-damascone\nGonzalez-Kristeller et al. (2015)","where":"reports/l2/fulltext/OLF-5.txt:99","row":true},{"text":"OR2T34\nfructone; cinnamaldehydefloralozonevanillin; α-damasconejasmonylestragole\nGonzalez-Kristeller et al. (2015)","where":"reports/l2/fulltext/OLF-5.txt:105","row":true}]}]},{"n":5,"id":"gprotein","title":"The receptor changes shape","text":"Bound, the receptor changes shape. On the inside of the membrane it activates its G protein, Golf, which splits in two: Gαolf, carrying GTP in place of GDP, and the pair Gβγolf. In the OR51E2 structure, the change that switches the receptor on runs through its third outer loop.","drawn":"One helix tilts outward; the drawing exaggerates the movement so it can be seen.","evidence":[{"source":"OLF-4","citation":"Genovese F, Reisert J, Kefalov VJ. Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics. Frontiers in Cellular Neuroscience 2021;15:761416. DOI 10.3389/fncel.2021.761416. PMCID PMC8531253.","url":"https://doi.org/10.3389/fncel.2021.761416","quotes":[{"text":"the ligand-activated OR proteins bind to the G protein Golf, causing its dissociation into active Gαolf and olfactory β- and γ-subunit, Gβγolf","where":"reports/l2/fulltext/OLF-4.txt:39","row":false},{"text":"the exchange of GDP for GTP on Gαolf and its activation","where":"reports/l2/fulltext/OLF-4.txt:49","row":false}]},{"source":"OLF-6","citation":"Billesbølle CB, de March CA, van der Velden WJC, Ma N, Tewari J, del Torrent CL, Li L, Faust B, Vaidehi N, Matsunami H, Manglik A. Structural basis of odorant recognition by a human odorant receptor. Nature 2023;615(7953):742–749. DOI 10.1038/s41586-023-05798-y. PMID 36922591. PMCID PMC10580732 (author manuscript).","url":"https://europepmc.org/articles/PMC10580732","quotes":[{"text":"Molecular dynamics simulations demonstrate that propionate-induced conformational changes in extracellular loop 3 activate OR51E2.","where":"docs/sources/OLF-6-billesbolle-2023-or51e2-structure.md:20","row":false}]}]},{"n":6,"id":"camp","title":"A messenger, cAMP","text":"Gαolf binds to an enzyme in the membrane, adenylyl cyclase 3, and switches it on. The enzyme makes cyclic AMP (cAMP), a messenger inside the cilium: one activated enzyme makes most likely hundreds of molecules. The receptor step itself adds no gain; the cAMP is where the signal grows.","drawn":"Nine cAMP molecules stand for hundreds.","evidence":[{"source":"OLF-4","citation":"Genovese F, Reisert J, Kefalov VJ. Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics. Frontiers in Cellular Neuroscience 2021;15:761416. DOI 10.3389/fncel.2021.761416. PMCID PMC8531253.","url":"https://doi.org/10.3389/fncel.2021.761416","quotes":[{"text":"Curiously, the activation of Golf by the OR molecule does not result in amplification.","where":"reports/l2/fulltext/OLF-4.txt:43","row":false},{"text":"Gαolf is part of the Gαs protein family and binds to adenylyl cyclase 3 (AC3), activating it. As a result, the synthesis of cAMP in the olfactory cilia is upregulated, causing its rapid increase and the opening of cAMP-gated channels","where":"reports/l2/fulltext/OLF-4.txt:39","row":false},{"text":"The activation of AC3 by Golf results in the synthesis of most likely hundreds of cAMP molecules","where":"reports/l2/fulltext/OLF-4.txt:43","row":false}]}]},{"n":7,"id":"channels","title":"Channels open","text":"cAMP opens the cyclic-nucleotide-gated (CNG) channels in the membrane, and sodium and calcium ions flow into the cilium. The calcium opens a second channel, Anoctamin 2, and chloride ions flow out. Both currents raise the voltage across the neuron’s membrane.","drawn":"Filled dots are sodium and calcium ions, open circles chloride; their number is illustrative.","evidence":[{"source":"OLF-4","citation":"Genovese F, Reisert J, Kefalov VJ. Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics. Frontiers in Cellular Neuroscience 2021;15:761416. DOI 10.3389/fncel.2021.761416. PMCID PMC8531253.","url":"https://doi.org/10.3389/fncel.2021.761416","quotes":[{"text":"In OSNs, the initial inward Na+ and Ca2+ current generated by the opening of the CNG channel raises ciliary Ca2+ and opens a secondary ion channel, the Ca2+-activated Cl− channel Anoctamin 2.","where":"reports/l2/fulltext/OLF-4.txt:40","row":false},{"text":"A high intraciliary Cl− maintained by the Na+/K+/2Cl− cotransporter 1 ensures a Cl− efflux which further depolarizes the OSNs","where":"reports/l2/fulltext/OLF-4.txt:40","row":false}]}]},{"n":8,"id":"spike","title":"A nerve signal","text":"The rise in voltage makes the neuron fire action potentials, brief electrical spikes that travel along its axon to the olfactory bulb of the brain. One molecule is not enough: a neuron needs around thirty binding events before it fires reliably.","drawn":"The voltage trace is drawn for the idea, not taken from a recording.","evidence":[{"source":"OLF-4","citation":"Genovese F, Reisert J, Kefalov VJ. Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics. Frontiers in Cellular Neuroscience 2021;15:761416. DOI 10.3389/fncel.2021.761416. PMCID PMC8531253.","url":"https://doi.org/10.3389/fncel.2021.761416","quotes":[{"text":"This depolarization triggers the generation of action potentials which further propagate along the axons, inducing glutamate release at synapses with the second order neurons in the olfactory bulb","where":"reports/l2/fulltext/OLF-4.txt:40","row":false},{"text":"cannot be activated by a single odorant molecule but instead require around 30 odorant binding events to begin firing action potentials reliably","where":"reports/l2/fulltext/OLF-4.txt:27","row":false}]}]},{"n":9,"id":"back","title":"Back to the perfume","text":"One odorant is recognised by several receptors, one receptor by several odorants, and different odorants by different combinations: the brain reads the pattern across many receptors, not a single one. Vanillin is one of the three components of this accord; labdanum absolute and frankincense are natural materials, each a mixture of molecules of its own, read by combinations of their own.","drawn":"The row of lit receptors is an illustrative pattern, not a measurement for vanillin or for any receptor.","evidence":[{"source":"OLF-7","citation":"Malnic B, Hirono J, Sato T, Buck LB. Combinatorial receptor codes for odors. Cell 1999;96(5):713–723. DOI 10.1016/S0092-8674(00)80581-4. PMID 10089886.","url":"https://doi.org/10.1016/S0092-8674(00)80581-4","quotes":[{"text":"We found that one OR recognizes multiple odorants and that one odorant is recognized by multiple ORs, but that different odorants are recognized by different combinations of ORs.","where":"docs/sources/OLF-7-malnic-1999-combinatorial-codes.md:15","row":false},{"text":"Thus, the olfactory system uses a combinatorial receptor coding scheme to encode odor identities.","where":"docs/sources/OLF-7-malnic-1999-combinatorial-codes.md:16","row":false}]},{"source":"OLF-6","citation":"Billesbølle CB, de March CA, van der Velden WJC, Ma N, Tewari J, del Torrent CL, Li L, Faust B, Vaidehi N, Matsunami H, Manglik A. Structural basis of odorant recognition by a human odorant receptor. Nature 2023;615(7953):742–749. DOI 10.1038/s41586-023-05798-y. PMID 36922591. PMCID PMC10580732 (author manuscript).","url":"https://europepmc.org/articles/PMC10580732","quotes":[{"text":"This task is accomplished by the combinatorial activation of approximately 400 odorant G protein-coupled receptors encoded in the human genome.","where":"docs/sources/OLF-6-billesbolle-2023-or51e2-structure.md:14","row":false}]},{"record":"material/labdanum-absolute","name":"labdanum absolute","href":"/material/labdanum-absolute","field":null,"value":null},{"record":"material/frankincense-resin","name":"frankincense","href":"/material/frankincense-resin","field":null,"value":null}]}],"limits":["No binding is measured here, and no receptor is identified: the receptor is a type, not a particular protein, and the pocket is drawn, not modeled from a structure.","The timing is the drawing’s, not the cell’s: binding lasts milliseconds, and the steps from receptor to spike run in a fraction of a second.","One molecule is followed for clarity; a neuron needs many binding events, and a smell is read across many neurons and many receptor types.","What vanillin smells like, or how strongly, is not shown: perception is read from the pattern, and the model draws no pattern for any particular odorant.","Nothing here is about health or about how a smell makes anyone feel."],"sources":["OLF-4","OLF-5","TXT-BUCK-AXEL-1991","OLF-6","OLF-7","TXT-BUCK-NOBEL","TXT-AXEL-NOBEL","NOBEL-3"]}