Cryo-EM structures of human bradykinin receptor-G<sub>q</sub> proteins complexes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35132089.
- Also identified by DOI 10.1038/s41467-022-28399-1 and PMC identifier 8821558.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>q</sub> 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<sup>6.48</sup>, 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<sub>q</sub> proteins. Our structures elucidate the molecular mechanisms for the ligand binding, receptor activation, and G<sub>q</sub> proteins coupling of B2R.
Medical subject headings
- GTP-Binding Protein alpha Subunits, Gq-G11
- Receptor, Bradykinin B2