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Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1

文献类型：期刊论文

作者Shao, Zhehua6; Shen, Qingya7,8,9; Yao, Bingpeng10,11; Mao, Chunyou7,8,9; Chen, Li-Nan7,8,9; Zhang, Huibing7,8,9; Shen, Dan-Dan7,8,9; Zhang, Chao6,12; Li, Weijie6; Du, Xufei6
刊名NATURE CHEMICAL BIOLOGY
出版日期2021-12-23
页码24
ISSN号1552-4450
DOI10.1038/s41589-021-00918-z
通讯作者Ying, Songmin(yings@zju.edu.cn) ; Zhang, Yan(zhang_yan@zju.edu.cn) ; Shen, Huahao(huahaoshen@zju.edu.cn)
英文摘要Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1-G(i) complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6-2.9 angstrom, illustrating the structural basis of natural biased signaling that initiates an inflammation response. Complemented with pharmacological and computational studies, these structures revealed it was the conformational change of Tyr291 (Y291(7.)(43)) in CCR1 that triggered its polar network rearrangement in the orthosteric binding pocket and allosterically regulated the activation of beta-arrestin signaling. Our structure of CCL15-bound CCR1 also exhibited a critical site for ligand binding distinct from many other chemokine-receptor complexes, providing new insights into the mode of chemokine recognition.
WOS关键词ACTIVATION ; RECOGNITION ; BINDING ; SYSTEM ; CELLS
资助项目National Natural Science Foundation of China[81930003] ; National Natural Science Foundation of China[82090012] ; National Natural Science Foundation of China[81922071] ; National Natural Science Foundation of China[81870007] ; National Natural Science Foundation of China[81920108001] ; Zhejiang Province National Science Fund[LR19H310001] ; Zhejiang Province National Science Fund[LD19H160001]
WOS研究方向Biochemistry & Molecular Biology
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:000733697400001
源URL[http://119.78.100.183/handle/2S10ELR8/300812]  
专题中国科学院上海药物研究所
通讯作者Ying, Songmin; Zhang, Yan; Shen, Huahao
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
2.Zhejiang Univ, Int Inst Med, Sch Med, Affiliated Hosp 4, Yiwu, Peoples R China
3.Zhejiang Prov Key Lab Immun & Inflammatory Dis, Hangzhou, Peoples R China
4.State Key Lab Resp Dis, Guangzhou, Peoples R China
5.Zhejiang Univ, MOE Frontier Sci Ctr Brain Res & Brain Machine In, Sch Med, Hangzhou, Peoples R China
6.Zhejiang Univ, Key Lab Resp Dis Zhejiang Prov, Dept Resp & Crit Care Med, Affiliated Hosp 2,Sch Med, Hangzhou, Peoples R China
7.Zhejiang Univ, Dept Biophys, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Peoples R China
8.Zhejiang Univ, Dept Pathol, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Peoples R China
9.Zhejiang Univ, Liangzhu Lab, Med Ctr, Hangzhou, Peoples R China
10.Zhejiang Univ, Affiliated Hosp 2, Dept Pharmacol, Key Lab Resp Dis Zhejiang Prov,Sch Med, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Shao, Zhehua,Shen, Qingya,Yao, Bingpeng,et al. Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1[J]. NATURE CHEMICAL BIOLOGY,2021:24.
APA Shao, Zhehua.,Shen, Qingya.,Yao, Bingpeng.,Mao, Chunyou.,Chen, Li-Nan.,...&Shen, Huahao.(2021).Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1.NATURE CHEMICAL BIOLOGY,24.
MLA Shao, Zhehua,et al."Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1".NATURE CHEMICAL BIOLOGY (2021):24.

入库方式： OAI收割

来源：上海药物研究所

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