Biology:TAS2R1
 Generic protein structure example |
Taste receptor type 2 member 1 (TAS2R1/T2R1) is a protein that in humans is encoded by the TAS2R1 gene.[1][2][3] It belongs to the G protein-coupled receptor (GPCR) family and is related to class A-like GPCRs, they contain 7 transmembrane helix bundles and short N-terminus loop.[4] Furthermore, TAS2R1 is member of the 25 known human bitter taste receptors, which enable the perception of bitter taste in the mouth cavity. Increasing evidence indicates a functional role of TAS2Rs in extra-oral tissues.[5]
Expression and function
Extra-oral roles of TAS2Rs
Bitter taste receptors are expressed in taste receptor cells, which organized into taste buds on the papillae of the tongue and palate epithelium.
In addition, TAS2Rs were found to be expressed in extra-oral tissues, e.g. brain, lungs, gastrointestinal tract, etc.[5] So far, less is known about their function however, for example it was shown that:
- TAS2Rs mediate relaxation of airway smooth muscles.[6]
- TAS2R43 is involved in secretion of gastric acid in the stomach.[7]
Extra-oral roles of TAS2R1
- TAS2R1, TAS2R4, TAS2R10, TAS2R38 and TAS2R49 were found to be down-regulated in breast cancer cells[8].
- TAS2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways[9].
Structure of TAS2R1 receptor
Based on a recent homology model from BitterDB[10][11] several conserved motifs, which are counterparts to Class A GPCRs[4] were found:
- Transmembrane helix 1: N1.50xxI1.53
- Transmembrane helix 2: L2.46xxxR2.50
- Transmembrane helix 3: F3.49Y3.50xxK3.53
- Transmembrane helix 5: P5.50
- Transmembrane helix 6: F6.44xxxY6.46
- Transmembrane helix 7: H7.49S7.50xxL7.53
Numbering is according to the Balleros-Weinstein[12] system.
Unlike in Class A GPCRs, in transmembrane helix 4 no DRY[13] motif was found as well as position 6.50 is not conserved.
TAS2R1 gene
This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a 7-transmembrane receptor protein, functioning as a bitter taste receptor.
SNPs
In T2R1 two SNPs are known in R111H and R206W (dbSNP).
Transcription Factors
So far, AML1a, AP-1, AREB6, FOXL1, IRF-7A, Lmo2, NF-E2, NF-E2 p45 were found as the top transcription factor binding sites by QIAGEN in the TAS2R1 gene promoter.
Mutagenesis data
Several mutations have been shown to influence binding of a ligand to TAS2R1 (based on BitterDB):
| Receptor region | BW number | Residue | Reference |
| TM1 | 1.5 | N24 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM1 | 1.53 | I27 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM2 | 2.5 | R55 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM2 | 2.56 | F61 | doi: 10.1074/jbc.M111.246983 |
| TM2 | 2.61 | N66 | doi: 10.3389/fmolb.2017.00063 doi: 10.1021/acs.jctc.5b00472 doi: 10.1016/bs.mcb.2015.10.005 doi: 10.1074/jbc.M111.246983 |
| ECL1 | E74 | doi: 10.3389/fmolb.2017.00063 | |
| TM3 | 3.32 | L85 | doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141 |
| TM3 | 3.33 | L86 | doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141 |
| TM3 | 3.36 | N89 | doi: 10.1016/bs.mcb.2015.10.005 doi: 10.1074/jbc.M111.246983 doi: doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM3 | 3.37 | E90 | doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141 |
| TM3 | 3.41 | W94 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM3 | 3.46 | L99 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM5 | 5.46 | E182 | doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141 |
| TM5 | 5.61 | L197 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM5 | 5.64 | S200 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM5 | 5.65 | L201 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM7 | 7.39 | I263 | doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141 |
| TM7 | 7.49 | H273 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM7 | 7.53 | L277 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
| TM7 | 7.54 | I278 | doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983 |
Ligands
Up to now, 39 ligands for T2R1 were identified (BitterDB), among them L-amino acids, peptides, humulones, small molecules etc.
See also
References
- ↑ "A novel family of mammalian taste receptors". Cell 100 (6): 693–702. Apr 2000. doi:10.1016/S0092-8674(00)80705-9. PMID 10761934.
- ↑ "A family of candidate taste receptors in human and mouse". Nature 404 (6778): 601–4. Apr 2000. doi:10.1038/35007072. PMID 10766242. Bibcode: 2000Natur.404..601M.
- ↑ "Entrez Gene: TAS2R1 taste receptor, type 2, member 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50834.
- ↑ 4.0 4.1 Di Pizio, Antonella; Levit, Anat; Slutzki, Michal; Behrens, Maik; Karaman, Rafik; Niv, Masha Y. (2016), "Comparing Class A GPCRs to bitter taste receptors", Methods in Cell Biology (Elsevier) 132: 401–427, doi:10.1016/bs.mcb.2015.10.005, ISBN 9780128035955, PMID 26928553
- ↑ 5.0 5.1 Lu, Ping; Zhang, Cheng-Hai; Lifshitz, Lawrence M.; ZhuGe, Ronghua (2017-01-04). "Extraoral bitter taste receptors in health and disease". The Journal of General Physiology 149 (2): 181–197. doi:10.1085/jgp.201611637. ISSN 0022-1295. PMID 28053191.
- ↑ Deshpande, Deepak A; Wang, Wayne C H; McIlmoyle, Elizabeth L; Robinett, Kathryn S; Schillinger, Rachel M; An, Steven S; Sham, James S K; Liggett, Stephen B (2010-10-24). "Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction". Nature Medicine 16 (11): 1299–1304. doi:10.1038/nm.2237. ISSN 1078-8956. PMID 20972434.
- ↑ Liszt, Kathrin Ingrid; Ley, Jakob Peter; Lieder, Barbara; Behrens, Maik; Stöger, Verena; Reiner, Angelika; Hochkogler, Christina Maria; Köck, Elke et al. (2017-07-10). "Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells". Proceedings of the National Academy of Sciences 114 (30): E6260–E6269. doi:10.1073/pnas.1703728114. ISSN 0027-8424. PMID 28696284.
- ↑ Singh, Nisha; Chakraborty, Raja; Bhullar, Rajinder Pal; Chelikani, Prashen (April 2014). "Differential expression of bitter taste receptors in non-cancerous breast epithelial and breast cancer cells". Biochemical and Biophysical Research Communications 446 (2): 499–503. doi:10.1016/j.bbrc.2014.02.140. ISSN 0006-291X. PMID 24613843.
- ↑ Upadhyaya, Jasbir D.; Singh, Nisha; Sikarwar, Anurag S.; Chakraborty, Raja; Pydi, Sai P.; Bhullar, Rajinder P.; Dakshinamurti, Shyamala; Chelikani, Prashen (2014-10-23). "Dextromethorphan Mediated Bitter Taste Receptor Activation in the Pulmonary Circuit Causes Vasoconstriction". PLoS ONE 9 (10): e110373. doi:10.1371/journal.pone.0110373. ISSN 1932-6203. PMID 25340739. Bibcode: 2014PLoSO...9k0373U.
- ↑ Wiener, Ayana; Shudler, Marina; Levit, Anat; Niv, Masha Y. (2011-09-22). "BitterDB: a database of bitter compounds". Nucleic Acids Research 40 (D1): D413–D419. doi:10.1093/nar/gkr755. ISSN 1362-4962. PMID 21940398.
- ↑ Dagan-Wiener, Ayana; Di Pizio, Antonella; Nissim, Ido; Bahia, Malkeet S; Dubovski, Nitzan; Margulis, Eitan; Niv, Masha Y (2018-10-24). "BitterDB: taste ligands and receptors database in 2019". Nucleic Acids Research 47 (D1): D1179–D1185. doi:10.1093/nar/gky974. ISSN 0305-1048. PMID 30357384.
- ↑ Ballesteros, Juan A.; Weinstein, Harel (1995), "[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors", Methods in Neurosciences (Elsevier): pp. 366–428, doi:10.1016/s1043-9471(05)80049-7, ISBN 9780121852955
- ↑ Rovati, G. E.; Capra, V.; Neubig, R. R. (2007-01-12). "The Highly Conserved DRY Motif of Class A G Protein-Coupled Receptors: Beyond the Ground State". Molecular Pharmacology 71 (4): 959–964. doi:10.1124/mol.106.029470. ISSN 0026-895X. PMID 17192495. https://semanticscholar.org/paper/a8d7aa739bb8c4825095ccbf2dd850d4077a664a.
Further reading
- Kinnamon SC (2000). "A plethora of taste receptors". Neuron 25 (3): 507–10. doi:10.1016/S0896-6273(00)81054-5. PMID 10774719.
- Margolskee RF (2002). "Molecular mechanisms of bitter and sweet taste transduction". J. Biol. Chem. 277 (1): 1–4. doi:10.1074/jbc.R100054200. PMID 11696554.
- "Receptors for bitter and sweet taste". Curr. Opin. Neurobiol. 12 (4): 366–71. 2002. doi:10.1016/S0959-4388(02)00345-8. PMID 12139982.
- "T2Rs function as bitter taste receptors". Cell 100 (6): 703–11. 2000. doi:10.1016/S0092-8674(00)80706-0. PMID 10761935.
- Firestein S (2000). "The good taste of genomics". Nature 404 (6778): 552–3. doi:10.1038/35007167. PMID 10766221.
- "Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways". Cell 112 (3): 293–301. 2003. doi:10.1016/S0092-8674(03)00071-0. PMID 12581520.
- "Evolution of bitter taste receptors in humans and apes". Mol. Biol. Evol. 22 (3): 432–6. 2005. doi:10.1093/molbev/msi027. PMID 15496549.
- "Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates". Genetics 170 (1): 313–26. 2006. doi:10.1534/genetics.104.037523. PMID 15744053.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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