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Molecular basis for kinin selectivity and activation of the human bradykinin receptors | |
Yin, Yu-Ling1,2; Ye, Chenyu; Zhou, Fulai1; Wang, Jia1,4; Yang, Dehua1,2,4; Yin, Wanchao1; Wang, Ming-Wei1,2,3,4,5,6; Xu, H. Eric1,2,5; Jiang, Yi1,2 | |
2021-09 | |
发表期刊 | NATURE STRUCTURAL & MOLECULAR BIOLOGY |
ISSN | 1545-9993 |
EISSN | 1545-9985 |
卷号 | 28期号:9页码:755-+ |
DOI | 10.1038/s41594-021-00645-y |
摘要 | Cryo-EM structures of human type 1 and type 2 bradykinin receptors (B1R and B2R) reveal the basis for discrimination between the endogenous peptides des-Arg(10)-kallidin and bradykinin and their activation mechanism. Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain control. Des-Arg(10)-kallidin, the carboxy-terminal des-Arg metabolite of kallidin, and bradykinin selectively activate two G protein-coupled receptors, type 1 and type 2 bradykinin receptors (B1R and B2R), respectively. The hyperactivation of bradykinin receptors, termed 'bradykinin storm', is associated with pulmonary edema in COVID-19 patients, suggesting that bradykinin receptors are important targets for COVID-19 intervention. Here we report two G protein-coupled complex structures of human B1R and B2R bound to des-Arg(10)-kallidin and bradykinin, respectively. Combined with functional analysis, our structures reveal the mechanism of ligand selectivity and specific activation of the bradykinin receptor. These findings also provide a framework for guiding drug design targeting bradykinin receptors for the treatment of inflammation, cardiovascular disorders and COVID-19. |
URL | 查看原文 |
收录类别 | SCIE |
语种 | 英语 |
WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
WOS类目 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
WOS记录号 | WOS:000698412300013 |
出版者 | NATURE PORTFOLIO |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128341 |
专题 | 生命科学与技术学院_特聘教授组_徐华强组 生命科学与技术学院_特聘教授组_王明伟组 |
通讯作者 | Yin, Wanchao; Wang, Ming-Wei; Xu, H. Eric; Jiang, Yi |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China; 2.Univ Chinese Acad Sci, Beijing, Peoples R China; 3.Fudan Univ, Sch Pharm, Shanghai, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai, Peoples R China; 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 6.Fudan Univ, Sch Basic Med Sci, Shanghai, Peoples R China |
通讯作者单位 | 生命科学与技术学院 |
推荐引用方式 GB/T 7714 | Yin, Yu-Ling,Ye, Chenyu,Zhou, Fulai,et al. Molecular basis for kinin selectivity and activation of the human bradykinin receptors[J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY,2021,28(9):755-+. |
APA | Yin, Yu-Ling.,Ye, Chenyu.,Zhou, Fulai.,Wang, Jia.,Yang, Dehua.,...&Jiang, Yi.(2021).Molecular basis for kinin selectivity and activation of the human bradykinin receptors.NATURE STRUCTURAL & MOLECULAR BIOLOGY,28(9),755-+. |
MLA | Yin, Yu-Ling,et al."Molecular basis for kinin selectivity and activation of the human bradykinin receptors".NATURE STRUCTURAL & MOLECULAR BIOLOGY 28.9(2021):755-+. |
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