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
ISSN1545-9993
EISSN1545-9985
卷号28期号:9页码:755-+
DOI10.1038/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.
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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
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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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