中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2

文献类型：期刊论文

作者Ke, Yudun6; Huang, Yimiao6; Yi, Cuiying; Ma, Limin2; Chu, Xiaojing2; Wu, Beili2,3,4,5,6; Zhao, Qiang1,2,3,6; Han, Shuo2,3,4,6
刊名CELL REPORTS
出版日期2024-12-24
卷号43期号:12页码:15
ISSN号2211-1247
DOI10.1016/j.celrep.2024.115024
英文摘要Free fatty acid receptors (FFARs) play critical roles in metabolic regulation and are potential therapeutic targets for metabolic and inflammatory diseases. A comprehensive understanding of the activation mechanisms and endogenous ligand selectivity of FFARs is essential for drug discovery. Here, we report two cryoelectron microscopy structures of the human FFAR1 bound to the endogenous ligand docosahexaenoic acid (DHA) and G i1 protein as well as FFAR2 in complex with butyrate and G i1 at 3.2 A & ring; and 3.3 A & ring; resolution, respectively. These structures highlight that distinct locations and sizes of the orthosteric ligand binding pockets are crucial determinants of the endogenous ligand selectivity of this receptor subfamily. Additionally, computational analysis reveals a potential allosteric ligand binding pocket in FFAR2. Furthermore, we observe that the upward movement of helix V upon endogenous ligand binding is responsible for receptor activation. These insights will significantly aid in the development of drugs targeting this receptor family.
WOS关键词CHAIN FATTY-ACIDS ; PROTEIN ; IDENTIFICATION ; METABOLITES ; GPR40
资助项目SA-SIBS Scholarship Program ; Youth Innovation Promotion Association CAS ; National Key R&D Program of China[2022YFA1302900] ; National Science Foundation of China[82121005] ; 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Cell Biology
WOS记录号WOS:001371857000001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/315001]  
专题新药研究国家重点实验室
通讯作者Wu, Beili; Zhao, Qiang; Han, Shuo
作者单位1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310058, Peoples R China
5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210046, Peoples R China
推荐引用方式
GB/T 7714		 Ke, Yudun,Huang, Yimiao,Yi, Cuiying,et al. Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2[J]. CELL REPORTS,2024,43(12):15.
APA Ke, Yudun.,Huang, Yimiao.,Yi, Cuiying.,Ma, Limin.,Chu, Xiaojing.,...&Han, Shuo.(2024).Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2.CELL REPORTS,43(12),15.
MLA Ke, Yudun,et al."Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2".CELL REPORTS 43.12(2024):15.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

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。