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ShanghaiTech University Knowledge Management System
| Unlocking TAS2R14 activation through intricate multi-ligand binding networks | |
| 2024-04-15 | |
| 状态 | 已发表 |
| 摘要 | Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1-3. In addition, TAS2R14 has broad expression in non-gustatory tissues, suggesting its important roles in selective physiological processes and therapeutic potential4. Here, we present cryo-electron microcopy structures of TAS2R14 in complex with flufenamic acid and aristolochic acid, coupling with G protein subtypes gustducin and Gi. Distinct from most known GPCRs, agonists of TAS2R14 bind to multiple intracellular pockets. We highlight the cholesterol molecules occupying an upper transmembrane site, typically the orthosteric pocket in other GPCRs, also binding in the entrance to an intracellular agonist binding pocket, suggesting an endogenous modulatory function5. The structural and mutagenesis analysis illuminate the receptor's broad-spectrum ligand recognition and activation via intricate multiple ligand-binding sites. Furthermore, we unveil the structural configuration of gustducin and its interaction with TAS2R14, as well as the coupling mode of Gi1. This investigation should be instrumental in advancing our knowledge of the mechanisms underlying bitter taste recognition and response, with broader relevance to sensory biology and pharmacology. |
| 语种 | 英语 |
| DOI | 10.1101/2024.04.13.589249 |
| 相关网址 | 查看原文 |
| 出处 | bioRxiv |
| 收录类别 | PPRN.PPRN |
| WOS记录号 | PPRN:88529018 |
| WOS类目 | Biophysics |
| 资助项目 | National Key Research and Development Program of China["Z200019","32230026","2022YFA1302902","XDB37030104"] ; National Natural Science Foundation of China["32271262","2019YFA0904200"] ; Key Research Project of the Beijing Natural Science Foundation[81773704] |
| 文献类型 | 预印本 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/372911 |
| 专题 | 生命科学与技术学院_博士生 生命科学与技术学院 iHuman研究所 iHuman研究所_公共科研平台_生命科学电镜平台 iHuman研究所_公共科研平台_昆虫细胞培养平台 iHuman研究所_公共科研平台_克隆平台 iHuman研究所_PI研究组_赵素文组 iHuman研究所_科学装置(X)_膜蛋白同步辐射线站 生命科学与技术学院_硕士生 iHuman研究所_PI研究组_华甜组 |
| 通讯作者 | Yang, Chi; Sun, Jinpeng; Hua, Tian; Liu, Zhi-Jie |
| 作者单位 | 1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Shandong Univ, Qilu Hosp, NHC Key Lab Otorhinolaryngol, Jinan 250012, Shandong, Peoples R China 4.Shandong Univ, Sch Basic Med Sci, Jinan 250012, Shandong, Peoples R China 5.Shanghai Ninth Peoples Hosp, Dept Oral Surg, Shanghai, Peoples R China 6.Shanghai Jiao Tong Univ, Coll Stomatol, Sch Med, Shanghai, Peoples R China 7.Chinese Acad Med Sci, Natl Ctr Stomatol, Beijing, Peoples R China 8.Chinese Acad Med Sci, Natl Clin Res Ctr Oral Dis, Shanghai Key Lab Stomatol, Beijing, Peoples R China 9.Chinese Acad Med Sci, Res Unit Oral & Maxillofacial Regenerat Med, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Xiaolong,Ao, Weizhen,Gao, Mingxin,et al. Unlocking TAS2R14 activation through intricate multi-ligand binding networks. 2024. |
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| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
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