ShanghaiTech University Knowledge Management System
Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1 | |
Qu, Xiangli1,2; Qiu, Na1,2; Wang, Mu1,3; Zhang, Bingjie4; Du, Juan5; Zhong, Zhiwei6; Xu, Wei1,2; Chu, Xiaojing1; Ma, Limin1; Yi, Cuiying1 | |
2022 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
卷号 | 604期号:7907页码:779-785 |
发表状态 | 已发表 |
DOI | 10.1038/s41586-022-04580-w |
摘要 | Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis(1-7). An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs(8,9), but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk-transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs. |
URL | 查看原文 |
收录类别 | SCI ; SCIE |
语种 | 英语 |
资助项目 | National Science Foundation of China[31825010,82121005,32171439,31971362] ; National Key R&D Program of China[2018YFA0507000] ; CAS Strategic Priority Research Program[XDB37030100] ; Shanghai Pilot Program for Basic Research-Chinese Academy of Sciences, Shanghai Branch[JCYJ-SHFY-2021-008] |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:000782392700004 |
出版者 | NATURE PORTFOLIO |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/176016 |
专题 | iHuman研究所_PI研究组_水雯箐组 生命科学与技术学院_特聘教授组_吴蓓丽组 生命科学与技术学院_博士生 |
通讯作者 | Shui, Wenqing; Zhao, Qiang; Wu, Beili |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, iHuman Inst, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 7.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China |
通讯作者单位 | 生命科学与技术学院 |
推荐引用方式 GB/T 7714 | Qu, Xiangli,Qiu, Na,Wang, Mu,et al. Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1[J]. NATURE,2022,604(7907):779-785. |
APA | Qu, Xiangli.,Qiu, Na.,Wang, Mu.,Zhang, Bingjie.,Du, Juan.,...&Wu, Beili.(2022).Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1.NATURE,604(7907),779-785. |
MLA | Qu, Xiangli,et al."Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1".NATURE 604.7907(2022):779-785. |
条目包含的文件 | 下载所有文件 | |||||
文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 |
个性服务 |
查看访问统计 |
谷歌学术 |
谷歌学术中相似的文章 |
[Qu, Xiangli]的文章 |
[Qiu, Na]的文章 |
[Wang, Mu]的文章 |
百度学术 |
百度学术中相似的文章 |
[Qu, Xiangli]的文章 |
[Qiu, Na]的文章 |
[Wang, Mu]的文章 |
必应学术 |
必应学术中相似的文章 |
[Qu, Xiangli]的文章 |
[Qiu, Na]的文章 |
[Wang, Mu]的文章 |
相关权益政策 |
暂无数据 |
收藏/分享 |
修改评论
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。