| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-09-02 |
| タイトル |
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|
タイトル |
Sugar binding of sodium–glucose cotransporters analyzed by voltage-clamp fluorometry |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 著者 |
watabe, erika
川鍋, 陽
神鳥, 和代
ichihara, satoko
藤原, 祐一郎
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Sugar absorption is crucial for life and relies on glucose transporters, including sodium–glucose cotransporters (SGLTs). Although the structure of SGLTs has been resolved, the substrate selectivity of SGLTs across diverse isoforms has not been determined owing to the complex substrate-recognition processes and limited analysis methods. Therefore, this study used voltage-clamp fluorometry (VCF) to explore the substrate-binding affinities of human SGLT1 in Xenopus oocytes. VCF analysis revealed high-affinity binding of D-glucose and D-galactose, which are known transported substrates. D-fructose, which is not a transported substrate, also bound to SGLT1, suggesting potential recognition despite the lack of transport activity. VCF analysis using the T287N mutant of the substrate-binding pocket, which has reduced D-glucose transport capacity, showed that its D-galactose-binding affinity exceeded its D-glucose-binding affinity. This suggests that the change in the VCF signal was due to substrate binding to the binding pocket. Both D-fructose and L-sorbose showed similar binding affinities, indicating that SGLT1 preferentially binds to pyranose-form sugars, including D-fructopyranose. Electrophysiological analysis confirmed that D-fructose binding did not affect the SGLT1 transport function. The significance of the VCF assay lies in its ability to measure sugar–protein interactions in living cells, thereby bridging the gap between structural analyses and functional characterizations of sugar transporters. Our findings also provide insights into SGLT substrate selectivity and the potential for developing medicines with reduced side effects by targeting non-glucose sugars with low bioreactivity. |
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言語 |
en |
| 書誌情報 |
en : Journal Of Biological Chemistry
巻 300,
号 5,
発行日 2024-05-01
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| 出版者 |
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出版者 |
Elsevier |
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言語 |
en |
| ISSN |
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収録物識別子タイプ |
PISSN |
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収録物識別子 |
1083-351X |
| 権利 |
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言語 |
en |
|
権利情報 |
© 2024 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. |
| 助成情報 |
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識別子タイプ |
Crossref Funder |
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助成機関識別子タイプURI |
https://www.crossref.org/services/funder-registry/ |
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助成機関識別子 |
https://doi.org/10.13039/501100001691 |
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助成機関名 |
日本学術振興会 |
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言語 |
ja |
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助成機関名 |
Japan Society for the Promotion of Science |
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言語 |
en |
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研究課題番号URI |
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-19K07301/ |
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研究課題番号 |
19K07301 |
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研究課題名 |
希少糖を用いたナトリウム・グルコース共輸送体の糖透過性の分子構造基盤解析 |
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言語 |
ja |
| 助成情報 |
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識別子タイプ |
Crossref Funder |
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助成機関識別子タイプURI |
https://www.crossref.org/services/funder-registry/ |
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助成機関識別子 |
https://doi.org/10.13039/501100001691 |
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助成機関名 |
日本学術振興会 |
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言語 |
ja |
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助成機関名 |
Japan Society for the Promotion of Science |
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言語 |
en |
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研究課題番号URI |
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PUBLICLY-21H05527/ |
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研究課題番号 |
21H05527 |
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研究課題名 |
弱い結合による糖の選択的吸収と血糖値の維持 公募研究 サマリー |
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言語 |
ja |
| PubMed番号 |
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関連タイプ |
isVersionOf |
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識別子タイプ |
PMID |
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関連識別子 |
38522518 |
| 著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
membrane transport |
| キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
sugar transport |
| キーワード |
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言語 |
en |
|
主題Scheme |
Other |
|
主題 |
structure-function |
| キーワード |
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言語 |
en |
|
主題Scheme |
Other |
|
主題 |
substrate specificity |
| キーワード |
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|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
voltage-clamp fluorometry |
| キーワード |
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|
言語 |
en |
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主題Scheme |
Other |
|
主題 |
SGLT |
| キーワード |
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|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
substrate recognition |