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-Structure paper
Title | Molecular basis for kinin selectivity and activation of the human bradykinin receptors. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 28, Issue 9, Page 755-761, Year 2021 |
Publish date | Sep 9, 2021 |
Authors | Yu-Ling Yin / Chenyu Ye / Fulai Zhou / Jia Wang / Dehua Yang / Wanchao Yin / Ming-Wei Wang / H Eric Xu / Yi Jiang / |
PubMed Abstract | 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 ...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-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-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. |
External links | Nat Struct Mol Biol / PubMed:34518695 |
Methods | EM (single particle) |
Resolution | 2.9 - 3.0 Å |
Structure data | EMDB-31145, PDB-7eib: EMDB-31429, PDB-7f2o: |
Source |
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Keywords | MEMBRANE PROTEIN / Bradykinin receptors / Kinin / GPCR / Complex |