Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-G(i) Complex Structures
Hua, Tian1; Li, Xiaoting1; Wu, Lijie1; Iliopoulos-Tsoutsouvas, Christos2,3; Wang, Yuxia1; Wu, Meng1,4; Shen, Ling1,4; Johnston, Christina A.5,6; Nikas, Spyros P.2,3; Song, Feng7
2020-02-20
发表期刊CELL
ISSN0092-8674
EISSN1097-4172
卷号180期号:4页码:655-+
发表状态已发表
DOI10.1016/j.cell.2020.01.008
摘要

Human endocannabinoid systems modulate multiple physiological processes mainly through the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low agonist selectivity, and lack of activation and G protein-coupling knowledge have hindered the development of therapeutic applications. Importantly, missing structural information has significantly held back the development of promising CB2-selective agonist drugs for treating inflammatory and neuropathic pain without the psychoactivity of CB1. Here, we report the cryoelectron microscopy structures of synthetic cannabinoid-bound CB2 and CB1 in complex with G(i), as well as agonist-bound CB2 crystal structure. Of important scientific and therapeutic benefit, our results reveal a diverse activation and signaling mechanism, the structural basis of CB2-selective agonists design, and the unexpected interaction of cholesterol with CB1, suggestive of its endogenous allosteric modulating role.

收录类别SCI ; SCIE
资助项目NIH[R01DA045020] ; NIH[R01DA041435] ; NIH[P01DA009158]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
WOS类目Biochemistry & Molecular Biology ; Cell Biology
WOS记录号WOS:000514846600005
出版者CELL PRESS
WOS关键词MOLECULAR-DYNAMICS ; MEMBRANE-PROTEINS ; CRYSTAL-STRUCTURE ; CB1 ; AGONIST ; SYSTEM ; INTEGRATION ; STRATEGY ; DOCKING ; MOTION
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/114838
专题生命科学与技术学院_硕士生
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_PI研究组_刘志杰组
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_博士生
iHuman研究所_PI研究组_华甜组
通讯作者Hua, Tian; Liu, Zhi-Jie
作者单位1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
2.Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA
3.Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
5.Scripps Res, Dept Mol Med, Jupiter, FL 33458 USA
6.Scripps Res, Dept Neurosci, Jupiter, FL 33458 USA
7.Dezhou Univ, Sch Life Sci, Dezhou 253023, Shandong, Peoples R China
8.Kunming Med Univ, Inst Mol & Clin Med, Kunming 650500, Yunnan, Peoples R China
9.Chinese Acad Sci, Shenzhen Inst Adv Technol, Res Ctr Comp Aided Drug Discovery, Shenzhen 518055, Peoples R China
10.Northeastern Univ, Dept Chem, Boston, MA 02115 USA
第一作者单位iHuman研究所
通讯作者单位iHuman研究所;  生命科学与技术学院
第一作者的第一单位iHuman研究所
推荐引用方式
GB/T 7714
Hua, Tian,Li, Xiaoting,Wu, Lijie,et al. Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-G(i) Complex Structures[J]. CELL,2020,180(4):655-+.
APA Hua, Tian.,Li, Xiaoting.,Wu, Lijie.,Iliopoulos-Tsoutsouvas, Christos.,Wang, Yuxia.,...&Liu, Zhi-Jie.(2020).Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-G(i) Complex Structures.CELL,180(4),655-+.
MLA Hua, Tian,et al."Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-G(i) Complex Structures".CELL 180.4(2020):655-+.
条目包含的文件
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
[Hua, Tian]的文章
[Li, Xiaoting]的文章
[Wu, Lijie]的文章
百度学术
百度学术中相似的文章
[Hua, Tian]的文章
[Li, Xiaoting]的文章
[Wu, Lijie]的文章
必应学术
必应学术中相似的文章
[Hua, Tian]的文章
[Li, Xiaoting]的文章
[Wu, Lijie]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

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。