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

doi:10.1038/s41589-021-00918-z

	Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1
	Shao, Zhehua 1; Shen, Qingya 2,3,4; Yao, Bingpeng 5,6; Mao, Chunyou 2,3,4; Chen, Li-Nan 2,3,4; Zhang, Huibing 2,3,4; Shen, Dan-Dan 2,3,4; Zhang, Chao 1,7; Li, Weijie 1; Du, Xufei 1; Li, Fei 1; Ma, Honglei 8,9; Chen, Zhi-Hua 1; Xu, H. Eric8,9,10 ; Ying, Songmin 5,6,11; Zhang, Yan 2,3,4,12,13; Shen, Huahao 1,14
	2022-03
发表期刊	NATURE CHEMICAL BIOLOGY
ISSN	1552-4450
EISSN	1552-4469
发表状态	已发表
DOI	10.1038/s41589-021-00918-z
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.
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[81930003,82090012,81922071,81870007,81920108001] ; Zhejiang Province National Science Fund["LR19H310001","LD19H160001"]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000733697400001
出版者	NATURE PORTFOLIO
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/145759
专题	生命科学与技术学院_特聘教授组_徐华强组
通讯作者	Ying, Songmin; Zhang, Yan; Shen, Huahao
作者单位	1.Zhejiang Univ, Key Lab Resp Dis Zhejiang Prov, Dept Resp & Crit Care Med, Affiliated Hosp 2,Sch Med, Hangzhou, Peoples R China 2.Zhejiang Univ, Dept Biophys, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Peoples R China 3.Zhejiang Univ, Dept Pathol, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Peoples R China 4.Zhejiang Univ, Liangzhu Lab, Med Ctr, Hangzhou, Peoples R China 5.Zhejiang Univ, Affiliated Hosp 2, Dept Pharmacol, Key Lab Resp Dis Zhejiang Prov,Sch Med, Hangzhou, Peoples R China 6.Zhejiang Univ, Affiliated Hosp 2, Dept Resp & Crit Care Med, Key Lab Resp Dis Zhejiang Prov,Sch Med, Hangzhou, Peoples R China 7.Zhejiang Univ, Dept Anat, Sch Med, Hangzhou, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Medica, CAS Key Lab Receptor Res, Shanghai, Peoples R China 9.Univ Chinese Acad Sci, Beijing, Peoples R China 10.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 11.Zhejiang Univ, Int Inst Med, Sch Med, Affiliated Hosp 4, Yiwu, Peoples R China 12.Zhejiang Prov Key Lab Immun & Inflammatory Dis, Hangzhou, Peoples R China 13.Zhejiang Univ, MOE Frontier Sci Ctr Brain Res & Brain Machine In, Sch Med, Hangzhou, Peoples R China 14.State Key Lab Resp Dis, Guangzhou, 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,2022.
APA	Shao, Zhehua.,Shen, Qingya.,Yao, Bingpeng.,Mao, Chunyou.,Chen, Li-Nan.,...&Shen, Huahao.(2022).Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1.NATURE CHEMICAL BIOLOGY.
MLA	Shao, Zhehua,et al."Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1".NATURE CHEMICAL BIOLOGY (2022).