Dimerization and substrate recognition of human taurine transporter
Abstract Taurine is a conditionally essential nutrient and one of the most abundant amino acids in humans, with diverse physiological functions. The cellular uptake of taurine is primarily mediated by the taurine transporter (TauT), and its dysfunction leads to retinal regeneration, cardiomyopathy,...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60967-z |
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| _version_ | 1849768995796811776 |
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| author | Yimin Zhang Jiahui Chen Nanhao Chen Haolin Xiong Zhengjiang Zhu Dongxue Yang Jingpeng Ge Jie Yu |
| author_facet | Yimin Zhang Jiahui Chen Nanhao Chen Haolin Xiong Zhengjiang Zhu Dongxue Yang Jingpeng Ge Jie Yu |
| author_sort | Yimin Zhang |
| collection | DOAJ |
| description | Abstract Taurine is a conditionally essential nutrient and one of the most abundant amino acids in humans, with diverse physiological functions. The cellular uptake of taurine is primarily mediated by the taurine transporter (TauT), and its dysfunction leads to retinal regeneration, cardiomyopathy, neurological and aging-associated disorders. Here we determine structures of TauT in two states: the apo inward-facing open state and the occluded state bound with substrate taurine or γ-aminobutyric acid (GABA). In addition to monomer, the structures also reveal a TauT dimer, where two cholesterol molecules act as “molecular glue”, and close contacts of two TM5 from each protomer mediate the dimer interface. In combination with functional characterizations, our results elucidate the detailed mechanisms of substrate recognition, specificity and transport by TauT, providing a structural framework for understanding TauT function and exploring potential therapeutic strategies for taurine-deficiency-related disorders. |
| format | Article |
| id | doaj-art-f2ec54c22e004340a3a6bc2a15d4e0c2 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f2ec54c22e004340a3a6bc2a15d4e0c22025-08-20T03:03:37ZengNature PortfolioNature Communications2041-17232025-07-0116111210.1038/s41467-025-60967-zDimerization and substrate recognition of human taurine transporterYimin Zhang0Jiahui Chen1Nanhao Chen2Haolin Xiong3Zhengjiang Zhu4Dongxue Yang5Jingpeng Ge6Jie Yu7Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesCenter for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking UniversityInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan UniversitySchool of Life Science and Technology, ShanghaiTech UniversityInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesAbstract Taurine is a conditionally essential nutrient and one of the most abundant amino acids in humans, with diverse physiological functions. The cellular uptake of taurine is primarily mediated by the taurine transporter (TauT), and its dysfunction leads to retinal regeneration, cardiomyopathy, neurological and aging-associated disorders. Here we determine structures of TauT in two states: the apo inward-facing open state and the occluded state bound with substrate taurine or γ-aminobutyric acid (GABA). In addition to monomer, the structures also reveal a TauT dimer, where two cholesterol molecules act as “molecular glue”, and close contacts of two TM5 from each protomer mediate the dimer interface. In combination with functional characterizations, our results elucidate the detailed mechanisms of substrate recognition, specificity and transport by TauT, providing a structural framework for understanding TauT function and exploring potential therapeutic strategies for taurine-deficiency-related disorders.https://doi.org/10.1038/s41467-025-60967-z |
| spellingShingle | Yimin Zhang Jiahui Chen Nanhao Chen Haolin Xiong Zhengjiang Zhu Dongxue Yang Jingpeng Ge Jie Yu Dimerization and substrate recognition of human taurine transporter Nature Communications |
| title | Dimerization and substrate recognition of human taurine transporter |
| title_full | Dimerization and substrate recognition of human taurine transporter |
| title_fullStr | Dimerization and substrate recognition of human taurine transporter |
| title_full_unstemmed | Dimerization and substrate recognition of human taurine transporter |
| title_short | Dimerization and substrate recognition of human taurine transporter |
| title_sort | dimerization and substrate recognition of human taurine transporter |
| url | https://doi.org/10.1038/s41467-025-60967-z |
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