7f2o

Publication Abstract from PubMed

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.

Molecular basis for kinin selectivity and activation of the human bradykinin receptors.,Yin YL, Ye C, Zhou F, Wang J, Yang D, Yin W, Wang MW, Xu HE, Jiang Y Nat Struct Mol Biol. 2021 Sep;28(9):755-761. doi: 10.1038/s41594-021-00645-y. , Epub 2021 Sep 9. PMID:34518695^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.