Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine
Abstract Taste is a key element for food palatability and is strongly influenced by the five basic tastes and other taste sensations, such as fatty orosensation, and koku perception, which indicates taste complexity, mouthfulness and lastingness. This study focuses on the taste modifier γ-glutamyl-v...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-87999-1 |
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| author | Hiroki Yamaguchi Seiji Kitajima Hiroshi Suzuki Shota Suzuki Kouki Nishikawa Akiko Kamegawa Yoshinori Fujiyoshi Kazutoshi Takahashi Uno Tagami Yutaka Maruyama Motonaka Kuroda Masayuki Sugiki |
| author_facet | Hiroki Yamaguchi Seiji Kitajima Hiroshi Suzuki Shota Suzuki Kouki Nishikawa Akiko Kamegawa Yoshinori Fujiyoshi Kazutoshi Takahashi Uno Tagami Yutaka Maruyama Motonaka Kuroda Masayuki Sugiki |
| author_sort | Hiroki Yamaguchi |
| collection | DOAJ |
| description | Abstract Taste is a key element for food palatability and is strongly influenced by the five basic tastes and other taste sensations, such as fatty orosensation, and koku perception, which indicates taste complexity, mouthfulness and lastingness. This study focuses on the taste modifier γ-glutamyl-valyl-glycine (γ-EVG), a potent kokumi substance that enhances taste and koku perception by modulating the calcium-sensing receptor (CaSR). We used cryo-electron microscopy to determine the structure of the CaSR/γ-EVG complex at a resolution of 3.55 Å. Structural analysis revealed important interactions between γ-EVG and the CaSR, involving key residues, such as Pro39, Phe42, Arg66, Ser147, and Glu297. Mutagenesis experiments demonstrated the importance of these residues in peptide binding. Each γ-EVG residue contributed to its binding to the orthosteric ligand binding site of the CaSR. These findings elucidate the molecular basis of kokumi peptide recognition by the CaSR and contribute to a better understanding of positive allosteric modulators of the CaSR. In addition, this research provides valuable insights into the functionality of class C G-protein-coupled receptors in taste perception, potentially informing the development of new taste modifiers and advancing the field of food science. |
| format | Article |
| id | doaj-art-c942862a087343599878e45ef291ed3f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c942862a087343599878e45ef291ed3f2025-02-02T12:19:33ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-87999-1Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycineHiroki Yamaguchi0Seiji Kitajima1Hiroshi Suzuki2Shota Suzuki3Kouki Nishikawa4Akiko Kamegawa5Yoshinori Fujiyoshi6Kazutoshi Takahashi7Uno Tagami8Yutaka Maruyama9Motonaka Kuroda10Masayuki Sugiki11Ajinomoto Co., Inc.Ajinomoto Co., Inc.Advanced Research Initiative, Institute of Integrated Research, Institute of Science TokyoAdvanced Research Initiative, Institute of Integrated Research, Institute of Science TokyoCeSPIA Inc.Advanced Research Initiative, Institute of Integrated Research, Institute of Science TokyoAdvanced Research Initiative, Institute of Integrated Research, Institute of Science TokyoAjinomoto Co., Inc.Ajinomoto Co., Inc.Ajinomoto Co., Inc.Ajinomoto Co., Inc.Ajinomoto Co., Inc.Abstract Taste is a key element for food palatability and is strongly influenced by the five basic tastes and other taste sensations, such as fatty orosensation, and koku perception, which indicates taste complexity, mouthfulness and lastingness. This study focuses on the taste modifier γ-glutamyl-valyl-glycine (γ-EVG), a potent kokumi substance that enhances taste and koku perception by modulating the calcium-sensing receptor (CaSR). We used cryo-electron microscopy to determine the structure of the CaSR/γ-EVG complex at a resolution of 3.55 Å. Structural analysis revealed important interactions between γ-EVG and the CaSR, involving key residues, such as Pro39, Phe42, Arg66, Ser147, and Glu297. Mutagenesis experiments demonstrated the importance of these residues in peptide binding. Each γ-EVG residue contributed to its binding to the orthosteric ligand binding site of the CaSR. These findings elucidate the molecular basis of kokumi peptide recognition by the CaSR and contribute to a better understanding of positive allosteric modulators of the CaSR. In addition, this research provides valuable insights into the functionality of class C G-protein-coupled receptors in taste perception, potentially informing the development of new taste modifiers and advancing the field of food science.https://doi.org/10.1038/s41598-025-87999-1Calcium-sensing receptorγ-Glutamyl-valyl-glycineClass C GPCRCryo-electron microscopySingle particle analysisKoku perception |
| spellingShingle | Hiroki Yamaguchi Seiji Kitajima Hiroshi Suzuki Shota Suzuki Kouki Nishikawa Akiko Kamegawa Yoshinori Fujiyoshi Kazutoshi Takahashi Uno Tagami Yutaka Maruyama Motonaka Kuroda Masayuki Sugiki Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine Scientific Reports Calcium-sensing receptor γ-Glutamyl-valyl-glycine Class C GPCR Cryo-electron microscopy Single particle analysis Koku perception |
| title | Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine |
| title_full | Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine |
| title_fullStr | Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine |
| title_full_unstemmed | Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine |
| title_short | Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine |
| title_sort | cryo em structure of the calcium sensing receptor complexed with the kokumi substance γ glutamyl valyl glycine |
| topic | Calcium-sensing receptor γ-Glutamyl-valyl-glycine Class C GPCR Cryo-electron microscopy Single particle analysis Koku perception |
| url | https://doi.org/10.1038/s41598-025-87999-1 |
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