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
Activation of the human chemokine receptor CX3CR1 regulated by cholesterol

文献类型：期刊论文

作者Lu, Minmin5,6,7; Zhao, Wenli5,6,7; Han, Shuo4,6,7; Lin, Xiaowen4,6,7; Xu, Tingyu5,6,7; Tan, Qiuxiang6,7; Wang, Mu3,6,7; Yi, Cuiying6,7; Chu, Xiaojing6,7; Yang, Weibo4,5,6
刊名SCIENCE ADVANCES
出版日期2022-07-01
卷号8期号:26页码:12
ISSN号2375-2548
DOI10.1126/sciadv.abn8048
通讯作者Zhu, Ya(zhuya2@simm.ac.cn) ; Wu, Beili(beiliwu@simm.ac.cn) ; Zhao, Qiang(zhaoq@simm.ac.cn)
英文摘要As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and neuropathy. However, the drug development of CX3CR1 is hampered partially by the lack of structural information. Here, we present two cryo-electron microscopy structures of CX3CR1-G(i1) complexes in ligand-free and CX3CL1-bound states at 2.8- and 3.4-angstrom resolution, respectively. Together with functional data, the structures reveal the key factors that govern the recognition of CX3CL1 by both CX3CR1 and US28. A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-G(i) complex structures is observed in CX3CR1, which may correlate with three cholesterol molecules that play essential roles in conformation stabilization and signaling transduction. Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor) signaling and provide insights into the diversity of G protein coupling.
WOS关键词STRUCTURAL BASIS ; FRACTALKINE/CX3CR1 ; IDENTIFICATION ; RECOGNITION ; MIGRATION ; MODULATOR ; BINDING ; POTENT ; CXCR4
资助项目National Key R&D Program of China[2018YFA0507000] ; CAS Strategic Priority Research Program[XDB37030100] ; National Science Foundation of China[31800618] ; National Science Foundation of China[31825010] ; National Science Foundation of China[82121005] ; 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
语种英语
WOS记录号WOS:000818943800017
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/301726]  
专题新药研究国家重点实验室
通讯作者Zhu, Ya; Wu, Beili; Zhao, Qiang
作者单位1.Chinese Acad Sci, SIMM, Zhongshan Inst Drug Discovery, Zhongshan, Peoples R China
2.Lingang Lab, Shanghai 200031, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
4.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China
5.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Lu, Minmin,Zhao, Wenli,Han, Shuo,et al. Activation of the human chemokine receptor CX3CR1 regulated by cholesterol[J]. SCIENCE ADVANCES,2022,8(26):12.
APA Lu, Minmin.,Zhao, Wenli.,Han, Shuo.,Lin, Xiaowen.,Xu, Tingyu.,...&Zhao, Qiang.(2022).Activation of the human chemokine receptor CX3CR1 regulated by cholesterol.SCIENCE ADVANCES,8(26),12.
MLA Lu, Minmin,et al."Activation of the human chemokine receptor CX3CR1 regulated by cholesterol".SCIENCE ADVANCES 8.26(2022):12.

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。