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![]() |
刊名 | CELL DISCOVERY
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出版日期 | 2022-05-15 |
卷号 | 8期号:1页码:11 |
DOI | 10.1038/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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