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TitleMolecular basis for kinin selectivity and activation of the human bradykinin receptors.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 9, Page 755-761, Year 2021
Publish dateSep 9, 2021
AuthorsYu-Ling Yin / Chenyu Ye / Fulai Zhou / Jia Wang / Dehua Yang / Wanchao Yin / Ming-Wei Wang / H Eric Xu / Yi Jiang /
PubMed AbstractBradykinin 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 linksNat Struct Mol Biol / PubMed:34518695
MethodsEM (single particle)
Resolution2.9 - 3.0 Å
Structure data

EMDB-31145, PDB-7eib:
Cryo-EM structure of the type 1 bradykinin receptor in complex with the des-Arg10-kallidin and an Gq protein
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-31429, PDB-7f2o:
Cryo-EM structure of the type 2 bradykinin receptor in complex with the bradykinin and an Gq protein
Method: EM (single particle) / Resolution: 2.9 Å

Source
  • homo sapiens (human)
  • rattus norvegicus (Norway rat)
  • bos taurus (cattle)
  • synthetic construct (others)
KeywordsMEMBRANE PROTEIN / Bradykinin receptors / Kinin / GPCR / Complex

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