Non-classical amine recognition evolved in a large clade of olfactory receptors
| العنوان: | Non-classical amine recognition evolved in a large clade of olfactory receptors |
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| المؤلفون: | Maude W. Baldwin, Qian Li, Yaw Tachie-Baffour, Zhikai Liu, Stephen D. Liberles, Andrew C. Kruse |
| المصدر: | eLife eLife, Vol 4 (2015) |
| بيانات النشر: | eLife Sciences Publications, Ltd, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Olfactory system, Tryptamine, Models, Molecular, QH301-705.5, Science, odorant receptors, Olfaction, Biology, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Receptors, G-Protein-Coupled, odorant receptor, Evolution, Molecular, chemistry.chemical_compound, ligand recognition, Animals, Biology (General), Amines, Receptor, Trace amine-associated receptor, Zebrafish, G protein-coupled receptor, General Immunology and Microbiology, molecular evolution, General Neuroscience, General Medicine, G Protein-Coupled Receptor, chemistry, Genomics and Evolutionary Biology, Medicine, Serotonin, Agmatine, Research Article, olfaction |
| الوصف: | Biogenic amines are important signaling molecules, and the structural basis for their recognition by G Protein-Coupled Receptors (GPCRs) is well understood. Amines are also potent odors, with some activating olfactory trace amine-associated receptors (TAARs). Here, we report that teleost TAARs evolved a new way to recognize amines in a non-classical orientation. Chemical screens de-orphaned eleven zebrafish TAARs, with agonists including serotonin, histamine, tryptamine, 2-phenylethylamine, putrescine, and agmatine. Receptors from different clades contact ligands through aspartates on transmembrane α-helices III (canonical Asp3.32) or V (non-canonical Asp5.42), and diamine receptors contain both aspartates. Non-classical monoamine recognition evolved in two steps: an ancestral TAAR acquired Asp5.42, gaining diamine sensitivity, and subsequently lost Asp3.32. Through this transformation, the fish olfactory system dramatically expanded its capacity to detect amines, ecologically significant aquatic odors. The evolution of a second, alternative solution for amine detection by olfactory receptors highlights the tremendous structural versatility intrinsic to GPCRs. DOI: http://dx.doi.org/10.7554/eLife.10441.001Test eLife digest Many organisms make molecules called biogenic amines. These molecules, which include the human hormones adrenaline and histamine, have important roles in regulating the biology and behaviour of many animals. Some biogenic amines bind to receptor proteins called GPCRs on the surface of cells. Many drugs can affect the activity of GPCRs, so understanding how different GPCRs work is an important goal of the pharmaceutical industry. Like all proteins, GPCRs are made of chains of molecules called amino acids. The GPCRs that can detect biogenic amines use a particular amino acid named Asp3.32, and when this amino acid is mutated, these GPCRs become unable to bind to their target amine. Trace amine-associated receptors (TAARs) are a type of GPCR that are found in many animals to detect odors. Most TAARs in mammals contain the Asp3.32 residue, and recognize amine odors. However, many fish TAARs do not contain Asp3.32, and it was not clear what molecules these fish receptors detect. Here Li et al. find that these fish TAARs also recognize amines, and use a different amino acid called Asp5.42. Also, some TAARs contain both Asp3.32 and Asp5.42, and recognize chemicals with two amines named diamines. Some diamines that bind to TAARs are foul smelling odors; for example, cadaverine and putrescine are repulsive smells emitted by decomposing flesh. In total, the experiments identified amines that can bind to eleven zebrafish TAARs that previously had no odor partner. Li et al. propose that some fish TAARs lost the Asp3.32 during the course of evolution to leave the Asp5.42 as the main interaction site for amines. This change dramatically altered how these TAARs interact with amines, which probably expanded the number of different amines that fish can detect. These findings open up new ways to study how the fish brain processes information about its surroundings. DOI: http://dx.doi.org/10.7554/eLife.10441.002Test |
| اللغة: | English |
| تدمد: | 2050-084X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b837a7be4e3c653c02b485271836763eTest http://europepmc.org/articles/PMC4695389Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b837a7be4e3c653c02b485271836763e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
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