7eib

Cryo-EM structure of the type 1 bradykinin receptor in complex with the des-Arg10-kallidin and an Gq proteinCryo-EM structure of the type 1 bradykinin receptor in complex with the des-Arg10-kallidin and an Gq protein

Structural highlights

7eib is a 5 chain structure with sequence from Bos taurus, Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BKRB1_HUMAN This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.^[1] ^[2]

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^[3]

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

References

↑ Menke JG, Borkowski JA, Bierilo KK, MacNeil T, Derrick AW, Schneck KA, Ransom RW, Strader CD, Linemeyer DL, Hess JF. Expression cloning of a human B1 bradykinin receptor. J Biol Chem. 1994 Aug 26;269(34):21583-6 PMID:8063797
↑ Bachvarov DR, Hess JF, Menke JG, Larrivée JF, Marceau F. Structure and genomic organization of the human B1 receptor gene for kinins (BDKRB1). Genomics. 1996 May 1;33(3):374-81. PMID:8660997 doi:10.1006/geno.1996.0213
↑ Yin YL, Ye C, Zhou F, Wang J, Yang D, Yin W, Wang MW, Xu HE, Jiang Y. Molecular basis for kinin selectivity and activation of the human bradykinin receptors. Nat Struct Mol Biol. 2021 Sep;28(9):755-761. PMID:34518695 doi:10.1038/s41594-021-00645-y

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Menke JG, Borkowski JA, Bierilo KK, MacNeil T, Derrick AW, Schneck KA, Ransom RW, Strader CD, Linemeyer DL, Hess JF. Expression cloning of a human B1 bradykinin receptor. J Biol Chem. 1994 Aug 26;269(34):21583-6 PMID:8063797

[2] Bachvarov DR, Hess JF, Menke JG, Larrivée JF, Marceau F. Structure and genomic organization of the human B1 receptor gene for kinins (BDKRB1). Genomics. 1996 May 1;33(3):374-81. PMID:8660997 doi:10.1006/geno.1996.0213

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

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