7F2O

Cryo-EM structure of the type 2 bradykinin receptor in complex with the bradykinin and an Gq protein

7F2O の概要

• エントリーDOI: 10.2210/pdb7f2o/pdb
• EMDBエントリー: 31429
• 分子名称: G subunit q (Gi1-Gq chimeric), Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ARG-PRO-PRO-GLY-PHE-SER-PRO-PHE-ARG, ... (6 entities in total)
• 機能のキーワード: gpcr, complex, membrane protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 185248.92

構造登録者

Yin, Y.,Jiang, Y. (登録日: 2021-06-11, 公開日: 2021-10-13, 最終更新日: 2025-07-02)

主引用文献

Yin, Y.L.,Ye, C.,Zhou, F.,Wang, J.,Yang, D.,Yin, W.,Wang, M.W.,Xu, H.E.,Jiang, Y.
Molecular basis for kinin selectivity and activation of the human bradykinin receptors.
Nat.Struct.Mol.Biol., 28:755-761, 2021

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 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.

PubMed: 34518695
DOI: 10.1038/s41594-021-00645-y

実験手法

ELECTRON MICROSCOPY (2.9 Å)