7xp5 › Citations

Structural basis for strychnine activation of human bitter taste receptor TAS2R46.

Xu W, Wu L, Liu S, Liu X, Cao X, Zhou C, Zhang J, Fu Y, Guo Y, Wu Y, Tan Q, Wang L, Liu J, Jiang L, Fan Z, Pei Y, Yu J, Cheng J, Zhao S, Hao X, Liu ZJ, Hua T
Science 377 1298-1304 (2022)
Related entries: 7xp4, 7xp6

Cited: 17 times
EuropePMC logo PMID: 36108005

Abstract

Taste sensing is a sophisticated chemosensory process, and bitter taste perception is mediated by type 2 taste receptors (TAS2Rs), or class T G protein-coupled receptors. Understanding the detailed molecular mechanisms behind taste sensation is hindered by a lack of experimental receptor structures. Here, we report the cryo-electron microscopy structures of human TAS2R46 complexed with chimeric mini-G protein gustducin, in both strychnine-bound and apo forms. Several features of TAS2R46 are disclosed, including distinct receptor structures that compare with known GPCRs, a new "toggle switch," activation-related motifs, and precoupling with mini-G protein gustducin. Furthermore, the dynamic extracellular and more-static intracellular parts of TAS2R46 suggest possible diverse ligand-recognition and activation processes. This study provides a basis for further exploration of other bitter taste receptors and their therapeutic applications.

Articles - 7xp5 mentioned but not cited (1)

  1. Activation Profile of TAS2R2, the 26th Human Bitter Taste Receptor. Lang T, Di Pizio A, Risso D, Drayna D, Behrens M. Mol Nutr Food Res 67 e2200775 (2023)


Reviews citing this publication (4)

  1. Bridging structural and cell biology with cryo-electron microscopy. Nogales E, Mahamid J. Nature 628 47-56 (2024)
  2. Structure, function and drug discovery of GPCR signaling. Cheng L, Xia F, Li Z, Shen C, Yang Z, Hou H, Sun S, Feng Y, Yong X, Tian X, Qin H, Yan W, Shao Z. Mol Biomed 4 46 (2023)
  3. Bitter Phytochemicals as Novel Candidates for Skin Disease Treatment. Grădinaru TC, Vlad A, Gilca M. Curr Issues Mol Biol 46 299-326 (2023)
  4. G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery. Zhang M, Chen T, Lu X, Lan X, Chen Z, Lu S. Signal Transduct Target Ther 9 88 (2024)

Articles citing this publication (12)

  1. Physiological activation of human and mouse bitter taste receptors by bile acids. Ziegler F, Steuer A, Di Pizio A, Behrens M. Commun Biol 6 612 (2023)
  2. Inhibiting a promiscuous GPCR: iterative discovery of bitter taste receptor ligands. Fierro F, Peri L, Hübner H, Tabor-Schkade A, Waterloo L, Löber S, Pfeiffer T, Weikert D, Dingjan T, Margulis E, Gmeiner P, Niv MY. Cell Mol Life Sci 80 114 (2023)
  3. Cryo-EM structure of the endothelin-1-ETB-Gi complex. Sano FK, Akasaka H, Shihoya W, Nureki O. Elife 12 e85821 (2023)
  4. Bitter taste receptor activation by cholesterol and an intracellular tastant. Kim Y, Gumpper RH, Liu Y, Kocak DD, Xiong Y, Cao C, Deng Z, Krumm BE, Jain MK, Zhang S, Jin J, Roth BL. Nature 628 664-671 (2024)
  5. Predicted structure and cell signaling of TAS2R14 reveal receptor hyper-flexibility for detecting diverse bitter tastes. Tokmakova A, Kim D, Guthrie B, Kim SK, Goddard WA, Liggett SB. iScience 26 106422 (2023)
  6. News A bitter taste receptor activated in a surprising way. Di Pizio A. Nature 628 506-507 (2024)
  7. Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors. Chen S, Zhou X, Lu Y, Xu K, Wen J, Cui M. Chem Senses 48 bjad035 (2023)
  8. Bitter taste sensitivity in domestic dogs (Canis familiaris) and its relevance to bitter deterrents of ingestion. Gibbs M, Winnig M, Riva I, Dunlop N, Waller D, Klebansky B, Logan DW, Briddon SJ, Holliday ND, McGrane SJ. PLoS One 17 e0277607 (2022)
  9. From Primary Data to Ethnopharmacological Investigations on Achillea erba-rotta subsp. moschata (Wulfen) I.Richardson as a Remedy against Gastric Ailments in Valmalenco (Italy). Bottoni M, Martinelli G, Maranta N, Sabato E, Milani F, Colombo L, Colombo PS, Piazza S, Sangiovanni E, Giuliani C, Bruschi P, Vistoli G, Dell'Agli M, Fico G. Plants (Basel) 13 539 (2024)
  10. Prediction of bitterness based on modular designed graph neural network. He Y, Liu K, Liu Y, Han W. Bioinform Adv 4 vbae041 (2024)
  11. Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts. Zhang Z, Zhou Z, Liu J, Zheng L, Peng X, Zhao L, Zheng X, Xu X. Front Immunol 15 1374900 (2024)
  12. VirtuousPocketome: a computational tool for screening protein-ligand complexes to identify similar binding sites. Pallante L, Cannariato M, Androutsos L, Zizzi EA, Bompotas A, Hada X, Grasso G, Kalogeras A, Mavroudi S, Di Benedetto G, Theofilatos K, Deriu MA. Sci Rep 14 6296 (2024)


Quick links