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  2. 上海药物研究所
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Identification of a carbohydrate recognition motif of purinergic receptors

文献类型：期刊论文

作者Zhao, Lifen2,4; Wei, Fangyu1,2,4; He, Xinheng1,2,4; Dai, Antao2,4; Yang, Dehua1,2,4; Jiang, Hualiang1,2,3,4; Wen, Liuqing1,2,4; Cheng, Xi1,2,3,4
刊名ELIFE
出版日期2023-11-13
卷号12页码:17
ISSN号2050-084X
关键词G-protein coupled receptor sugar nucleotide recogonition mechanism functional motif Human
DOI10.7554/eLife.85449
通讯作者Wen, Liuqing(lwen@simm.ac.cn) ; Cheng, Xi(xicheng@simm.ac.cn)
英文摘要As a major class of biomolecules, carbohydrates play indispensable roles in various biological processes. However, it remains largely unknown how carbohydrates directly modulate important drug targets, such as G-protein coupled receptors (GPCRs). Here, we employed P2Y purinoceptor 14 (P2Y14), a drug target for inflammation and immune responses, to uncover the sugar nucleotide activation of GPCRs. Integrating molecular dynamics simulation with functional study, we identified the uridine diphosphate (UDP)-sugar-binding site on P2Y14, and revealed that a UDP-glucose might activate the receptor by bridging the transmembrane (TM) helices 2 and 7. Between TM2 and TM7 of P2Y14, a conserved salt bridging chain (K-2.60-D-2.64-K-7.35-E-7.36 [KDKE]) was identified to distinguish different UDP-sugars, including UDP-glucose, UDP-galactose, UDP-glucuronic acid, and UDP-N-acetylglucosamine. We identified the KDKE chain as a conserved functional motif of sugar binding for both P2Y14 and P2Y purinoceptor 12 (P2Y12), and then designed three sugar nucleotides as agonists of P2Y12. These results not only expand our understanding for activation of purinergic receptors but also provide insights for the carbohydrate drug development for GPCRs.
WOS关键词FACILE ENZYMATIC-SYNTHESIS ; NEUTROPHIL RECRUITMENT ; CHEMOTAXIS ; ANTAGONIST ; ACTIVATION ; DISCOVERY ; EFFICIENT ; DYNAMICS ; AGONIST
资助项目Shanghai Municipal Science and Technology Major Project ; Lingang Laboratory grant[LG202102-01-01] ; Lingang Laboratory grant[LG-QS-202206-08] ; Fund of Youth Innovation Promotion Association[2022077] ; National Key Research and Development Program of China[2021YFA1301900] ; National Natural Science Foundation of China[22007092]
WOS研究方向Life Sciences & Biomedicine - Other Topics
语种英语
出版者eLIFE SCIENCES PUBL LTD
WOS记录号WOS:001134627000001
源URL[http://119.78.100.183/handle/2S10ELR8/308511]  
专题新药研究国家重点实验室
通讯作者Wen, Liuqing; Cheng, Xi
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Chinese Acad Sci, Carbohydrate Based Drug Res Ctr, State Key Lab Drug Res, Shanghai, Peoples R China
3.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhao, Lifen,Wei, Fangyu,He, Xinheng,et al. Identification of a carbohydrate recognition motif of purinergic receptors[J]. ELIFE,2023,12:17.
APA Zhao, Lifen.,Wei, Fangyu.,He, Xinheng.,Dai, Antao.,Yang, Dehua.,...&Cheng, Xi.(2023).Identification of a carbohydrate recognition motif of purinergic receptors.ELIFE,12,17.
MLA Zhao, Lifen,et al."Identification of a carbohydrate recognition motif of purinergic receptors".ELIFE 12(2023):17.

入库方式： OAI收割

来源：上海药物研究所

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