7F6H

Cryo-EM structure of human bradykinin receptor BK2R in complex Gq proteins and bradykinin

Summary for 7F6H

• Entry DOI: 10.2210/pdb7f6h/pdb
• EMDB information: 31480
• Descriptor: Bradykinin receptor BK2R, Bradykinin, Guanine nucleotide-binding protein G(q) subunit alpha, ... (6 entities in total)
• Functional Keywords: gpcr, bradykinin receptor, membrane protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 5
• Total formula weight: 180163.97

Authors

Shen, J.,Zhang, D.,Fu, Y.,Chen, A.,Zhang, H. (deposition date: 2021-06-25, release date: 2022-01-05, Last modification date: 2024-10-23)

Primary citation

Shen, J.,Zhang, D.,Fu, Y.,Chen, A.,Yang, X.,Zhang, H.
Cryo-EM structures of human bradykinin receptor-G q proteins complexes.
Nat Commun, 13:714-714, 2022

PubMed Abstract: The type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin and kallidin are both endogenous peptide agonists of B2R, acting as vasodilators to protect the cardiovascular system. Here we determine two cryo-electron microscopy (cryo-EM) structures of human B2R-G in complex with bradykinin and kallidin at 3.0 Å and 2.9 Å resolution, respectively. The ligand-binding pocket accommodates S-shaped peptides, with aspartic acids and glutamates as an anion trap. The phenylalanines at the tail of the peptides induce significant conformational changes in the toggle switch W283, the conserved PIF, DRY, and NPxxY motifs, for the B2R activation. This further induces the extensive interactions of the intracellular loops ICL2/3 and helix 8 with G proteins. Our structures elucidate the molecular mechanisms for the ligand binding, receptor activation, and G proteins coupling of B2R.

PubMed: 35132089
DOI: 10.1038/s41467-022-28399-1

Experimental method

ELECTRON MICROSCOPY (2.9 Å)