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  2. 上海药物研究所
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  4. 新药研究国家重点实验室
Structural insights into ligand recognition, selectivity, and activation of bombesin receptor subtype-3

文献类型：期刊论文

作者Li, Changyao5,6,7; Xu, Youwei7; Su, Wenxin3,4; He, Xinheng2,7; Li, Jingru1; Li, Xinzhu1; Xu, H. Eric1,2,5,6,7; Yin, Wanchao2,3,4,7
刊名CELL REPORTS
出版日期2024-08-27
卷号43期号:8页码:20
ISSN号2211-1247
DOI10.1016/j.celrep.2024.114511
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Yin, Wanchao(wcyin@simm.ac.cn)
英文摘要Bombesin receptor subtype-3 (BRS3) is an important orphan G protein-coupled receptor that regulates energy homeostasis and insulin secretion. As a member of the bombesin receptor (BnR) family, the lack of known endogenous ligands and high-resolution structure has hindered the understanding of BRS3 signaling and function. We present two cryogenic electron microscopy (cryo-EM) structures of BRS3 in complex with the heterotrimeric Gq q protein in its active states: one bound to the pan-BnR agonist BA1 and the other bound to the synthetic BRS3-specific agonist MK-5046. These structures reveal the architecture of the orthosteric ligand pocket underpinning molecular recognition and provide insights into the structural basis for BRS3's selectivity and low affinity for bombesin peptides. Examination of conserved micro-switches suggests a shared activation mechanism among BnRs. Our findings shed light on BRS3's ligand selectivity and signaling mechanisms, paving the way for exploring its therapeutic potential for diabetes, obesity, and related metabolic disorders.
WOS关键词GASTRIN-RELEASING-PEPTIDE ; MOLECULAR-BASIS ; HIGH-AFFINITY ; AGONIST ; PHARMACOLOGY ; DISCOVERY ; MK-5046 ; EXPRESSION ; CLONING ; POTENT
资助项目National Key R&D Program of China[2023YFC3605504] ; Youth Innovation Promotion Association of CAS[2021278] ; National Natural Science Foundation of China[32171189] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; National Science Fund for Excellent Young Scholars[82122067] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2023010] ; CAS[XDB37030103] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Lingang Laboratory[LG-GG-202204-01] ; High-level new R&D institute from Department of Science and Technology of Guangdong Province[2019B090904008] ; High-level Innovative Research Institute from Department of Science and Technology of Guangdong Province[2021B0909050003] ; Sanofi Scholarship Program
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001274644800001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/312523]  
专题新药研究国家重点实验室
通讯作者Xu, H. Eric; Yin, Wanchao
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China
4.Guangzhou Univ Chinese Med, Zhongshan Inst Drug Discovery, Guangzhou 510000, Guangdong, Peoples R China
5.Lingang Lab, Shanghai 200031, Peoples R China
6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Li, Changyao,Xu, Youwei,Su, Wenxin,et al. Structural insights into ligand recognition, selectivity, and activation of bombesin receptor subtype-3[J]. CELL REPORTS,2024,43(8):20.
APA Li, Changyao.,Xu, Youwei.,Su, Wenxin.,He, Xinheng.,Li, Jingru.,...&Yin, Wanchao.(2024).Structural insights into ligand recognition, selectivity, and activation of bombesin receptor subtype-3.CELL REPORTS,43(8),20.
MLA Li, Changyao,et al."Structural insights into ligand recognition, selectivity, and activation of bombesin receptor subtype-3".CELL REPORTS 43.8(2024):20.

入库方式： OAI收割

来源：上海药物研究所

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