中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3

文献类型:期刊论文

作者Shao, Zhehua14; Tan, Yangxia11,12,13; Shen, Qingya8,9,10; Hou, Li11,13; Yao, Bingpeng7,14; Qin, Jiao8,9,10; Xu, Peiyu11,13; Mao, Chunyou8,9,10; Chen, Li-Nan8,9,10; Zhang, Huibing8,9,10
刊名CELL DISCOVERY
出版日期2022-05-15
卷号8期号:1页码:11
DOI10.1038/s41421-022-00403-4
通讯作者Ying, Songmin(yings@zju.edu.cn) ; Ma, Honglei(mahonglei@sdu.edu.cn) ; Zhang, Yan(zhang_yan@zju.edu.cn) ; Shen, Huahao(huahuahao@zju.edu.cn)
英文摘要Chemokine receptors are a family of G-protein-coupled receptors with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures of two human CC chemokine receptor-G-protein complexes: CCR2 bound to its endogenous ligand CCL2, and CCR3 in the apo state. The structure of the CCL2-CCR2-G-protein complex reveals that CCL2 inserts deeply into the extracellular half of the transmembrane domain, and forms substantial interactions with the receptor through the most N-terminal glutamine. Extensive hydrophobic and polar interactions are present between both two chemokine receptors and the G alpha-protein, contributing to the constitutive activity of these receptors. Notably, complemented with functional experiments, the interactions around intracellular loop 2 of the receptors are found to be conserved and play a more critical role in G-protein activation than those around intracellular loop 3. Together, our findings provide structural insights into chemokine recognition and receptor activation, shedding lights on drug design targeting chemokine receptors.
WOS关键词MONOCLONAL-ANTIBODY ; INHIBITION ; MECHANISM ; CELLS ; MODEL
资助项目National Natural Science Foundation of China[81930003] ; National Natural Science Foundation of China[81922071] ; National Natural Science Foundation of China[81870007] ; National Natural Science Foundation of China[81920108001] ; National Natural Science Foundation of China[31770796] ; Zhejiang Province National Science Fund[LR19H310001] ; Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents[2016-63] ; Ministry of Science and Technology of China[2018YFA0507002] ; Strategic Priority Research Program of Chinese Academy of Science[XDB37030103] ; Shanghai Municipal Science and Technology Major Projects[2019SHZDZX02] ; Shandong University Qilu Young Scholar[62450082163091] ; Shanghai Municipal Science and Technology Commission[19ZR1467500] ; Young Innovator Association of CAS Enrollment ; MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000795870300001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/301077]  
专题中国科学院上海药物研究所
通讯作者Ying, Songmin; Ma, Honglei; Zhang, Yan; Shen, Huahao
作者单位1.State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China
2.Zhejiang Univ, MOE Frontier Sci Ctr Brain Res & Brain Machine In, Sch Med, Hangzhou, Zhejiang, Peoples R China
3.Zhejiang Prov Key Lab Immun & Inflammatory Dis, Hangzhou, Zhejiang, Peoples R China
4.Shandong Univ, State Key Lab Microbial Technol, Qingdao, Shandong, Peoples R China
5.Zhejiang Univ, Sch Med, Affiliated Hosp 4, Int Inst Med, Yiwu, Zhejiang, Peoples R China
6.Zhejiang Univ, Dept Anat, Sch Med, Hangzhou, Zhejiang, Peoples R China
7.Zhejiang Univ, Dept Pharmacol, Sch Med, Affiliated Hosp 2,Key Lab Resp Dis Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China
8.Zhejiang Univ, Liangzhu Lab, Med Ctr, Hangzhou, Zhejiang, Peoples R China
9.Zhejiang Univ, Dept Pathol, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China
10.Zhejiang Univ, Dept Biophys, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714
Shao, Zhehua,Tan, Yangxia,Shen, Qingya,et al. Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3[J]. CELL DISCOVERY,2022,8(1):11.
APA Shao, Zhehua.,Tan, Yangxia.,Shen, Qingya.,Hou, Li.,Yao, Bingpeng.,...&Shen, Huahao.(2022).Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3.CELL DISCOVERY,8(1),11.
MLA Shao, Zhehua,et al."Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3".CELL DISCOVERY 8.1(2022):11.

入库方式: OAI收割

来源:上海药物研究所

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