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TitleCryo-EM structures of human bradykinin receptor-G proteins complexes.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 714, Year 2022
Publish dateFeb 7, 2022
AuthorsJinkang Shen / Dongqi Zhang / Yao Fu / Anqi Chen / Xiaoli Yang / Haitao Zhang /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:35132089 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 2.9 Å
Structure data

31480

7f6h

EMDB-31480, PDB-7f6h:
Cryo-EM structure of human bradykinin receptor BK2R in complex Gq proteins and bradykinin
Method: EM (single particle) / Resolution: 2.9 Å

31481

7f6i

EMDB-31481, PDB-7f6i:
Cryo-EM structure of human bradykinin receptor BK2R in complex Gq proteins and kallidin
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL / Cholesterol

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / GPCR / bradykinin receptor

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