The B2 receptor (B2R) is aG protein-coupled receptor, probably coupled toGq andGi. A 2022Naturecryo-EM study of human B2R-Gq complexes by Jinkeng Sheng et al. investigated the proximal activation mechanisms of B2R. Sheng et al. propose that upon B2R binding bradykinin or kallidin to a "bulky orthosteric binding pocket," the phenylalanine F8 or F9 residue of bradykinin or kallidin respectively interacts with a "conserved toggle switch"W283. This hydrophobic interaction facilitates the outward movement of transmembrane domain 6 (TM6) of B2R on the cytoplasmic side of the membrane, as well as outward movement of F279, a key residue within the conservedPIF motif of GPCRs (involving proline, isoleucine and phenylalanine). This rearrangement of the PIF motif disrupts the ionic lock formed by theDRY motif and pushes theNPxxY motif towards the activated state, opening an "intracellular cleft" for insertion of the α5-helix of Gq.[5]
The B2 receptor forms a complex with angiotensin converting enzyme (ACE), and this is thought to play a role in cross-talk between the renin-angiotensin system (RAS) and thekinin–kallikrein system (KKS). The heptapeptideangiotensin (1-7) also potentiates bradykinin action on B2 receptors.[6]
Kallidin also signals through the B2 receptor. An antagonist for the receptor is Hoe 140 (icatibant).[7]
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