Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein.
Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS) and a neocul...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3084864?pdf=render |
| _version_ | 1818412336853024768 |
|---|---|
| author | Ken-ichiro Nakajima Kanako Yokoyama Taichi Koizumi Ayako Koizumi Tomiko Asakura Tohru Terada Katsuyoshi Masuda Keisuke Ito Akiko Shimizu-Ibuka Takumi Misaka Keiko Abe |
| author_facet | Ken-ichiro Nakajima Kanako Yokoyama Taichi Koizumi Ayako Koizumi Tomiko Asakura Tohru Terada Katsuyoshi Masuda Keisuke Ito Akiko Shimizu-Ibuka Takumi Misaka Keiko Abe |
| author_sort | Ken-ichiro Nakajima |
| collection | DOAJ |
| description | Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS) and a neoculin basic subunit (NBS). Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s) responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor-taste substance in particular. |
| first_indexed | 2024-12-14T10:45:42Z |
| format | Article |
| id | doaj.art-fed92306d05f4ee3a342a13fcd90c9f7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T10:45:42Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fed92306d05f4ee3a342a13fcd90c9f72022-12-21T23:05:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0164e1944810.1371/journal.pone.0019448Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein.Ken-ichiro NakajimaKanako YokoyamaTaichi KoizumiAyako KoizumiTomiko AsakuraTohru TeradaKatsuyoshi MasudaKeisuke ItoAkiko Shimizu-IbukaTakumi MisakaKeiko AbeNeoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS) and a neoculin basic subunit (NBS). Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s) responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor-taste substance in particular.http://europepmc.org/articles/PMC3084864?pdf=render |
| spellingShingle | Ken-ichiro Nakajima Kanako Yokoyama Taichi Koizumi Ayako Koizumi Tomiko Asakura Tohru Terada Katsuyoshi Masuda Keisuke Ito Akiko Shimizu-Ibuka Takumi Misaka Keiko Abe Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein. PLoS ONE |
| title | Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein. |
| title_full | Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein. |
| title_fullStr | Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein. |
| title_full_unstemmed | Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein. |
| title_short | Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein. |
| title_sort | identification and modulation of the key amino acid residue responsible for the ph sensitivity of neoculin a taste modifying protein |
| url | http://europepmc.org/articles/PMC3084864?pdf=render |
| work_keys_str_mv | AT kenichironakajima identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT kanakoyokoyama identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT taichikoizumi identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT ayakokoizumi identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT tomikoasakura identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT tohruterada identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT katsuyoshimasuda identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT keisukeito identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT akikoshimizuibuka identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT takumimisaka identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein AT keikoabe identificationandmodulationofthekeyaminoacidresidueresponsibleforthephsensitivityofneoculinatastemodifyingprotein |