Biology:Bradykinin receptor B2

From HandWiki
Short description: Protein found in humans

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Bradykinin receptor B2 is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans.

Mechanism

The B2 receptor (B2R) is a G protein-coupled receptor, probably coupled to Gq and Gi. A 2022 Nature cryo-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 conserved PIF motif of GPCRs (involving proline, isoleucine and phenylalanine). This rearrangement of the PIF motif disrupts the ionic lock formed by the DRY motif and pushes the NPxxY motif towards the activated state, opening an "intracellular cleft" for insertion of the α5-helix of Gq.[1]

Gq stimulates phospholipase C to increase intracellular free calcium and Gi inhibits adenylate cyclase. Furthermore, the receptor stimulates the mitogen-activated protein kinase pathways. It is ubiquitously and constitutively expressed in healthy tissues.

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 the kinin–kallikrein system (KKS). The heptapeptide angiotensin (1-7) also potentiates bradykinin action on B2 receptors.[2]

Kallidin also signals through the B2 receptor. Antagonists for the receptor are Hoe 140/icatibant), Deucrictibant.[3]

Function

The 9 amino acid bradykinin peptide elicits several responses including vasodilation, edema, smooth muscle spasm and nociceptor stimulation.

Gene

Alternate start codons result in two isoforms of the protein.[4]

See also

References

  1. ↑ "Cryo-EM structures of human bradykinin receptor-Gq proteins complexes". Nature Communications 13 (1). February 2022. doi:10.1038/s41467-022-28399-1. PMID 35132089. Bibcode: 2022NatCo..13..714S. 
  2. ↑ "Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo". Hypertension 37 (2 Pt 2): 703–709. February 2001. doi:10.1161/01.hyp.37.2.703. PMID 11230360. 
  3. ↑ "Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies". British Journal of Pharmacology 102 (3): 774–777. March 1991. doi:10.1111/j.1476-5381.1991.tb12249.x. PMID 1364852. 
  4. ↑ "Entrez Gene: BDKRB2 bradykinin receptor B2". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=624. 

Further reading

  • "[30 years: Happy birthday, GPCR. The bradykinin B2 receptor: an alternative and antiproliferative pathway]". Nephrologie 23 (1): 39–41. 2002. PMID 11908480. 
  • "[Endothelin 1 and angiotensin II in preeeclampsia]". Revista de Investigacion Clinica 59 (1): 48–56. 2007. PMID 17569300. 
  • "Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor". Biochemical and Biophysical Research Communications 184 (1): 260–268. April 1992. doi:10.1016/0006-291X(92)91187-U. PMID 1314587. Bibcode: 1992BBRC..184..260H. 
  • "Molecular cloning, functional expression and pharmacological characterization of a human bradykinin B2 receptor gene". Biochemical and Biophysical Research Communications 187 (3): 1306–1313. September 1992. doi:10.1016/0006-291X(92)90445-Q. PMID 1329734. Bibcode: 1992BBRC..187.1306E. 
  • "The human bradykinin B2 receptor gene: full length cDNA, genomic organization and identification of the regulatory region". Biochemical and Biophysical Research Communications 211 (1): 226–233. June 1995. doi:10.1006/bbrc.1995.1800. PMID 7779089. 
  • "Identification of polymorphic sites of the human bradykinin B2 receptor gene". Biochemical and Biophysical Research Communications 211 (1): 234–240. June 1995. doi:10.1006/bbrc.1995.1801. PMID 7779090. 
  • "Structure and chromosomal localization of the gene (BDKRB2) encoding human bradykinin B2 receptor". Genomics 23 (2): 362–369. September 1994. doi:10.1006/geno.1994.1512. PMID 7835885. 
  • "Human bradykinin B2 receptor: nucleotide sequence analysis and assignment to chromosome 14". Genomics 15 (2): 435–438. February 1993. doi:10.1006/geno.1993.1084. PMID 7916737. 
  • "Expression cloning of a human B1 bradykinin receptor". The Journal of Biological Chemistry 269 (34): 21583–21586. August 1994. doi:10.1016/S0021-9258(17)31844-6. PMID 8063797. 
  • "Differential pharmacology of cloned human and mouse B2 bradykinin receptors". Molecular Pharmacology 45 (1): 1–8. January 1994. doi:10.1016/S0026-895X(25)09890-6. PMID 8302267. 
  • "Cloned murine bradykinin receptor exhibits a mixed B1 and B2 pharmacological selectivity". Molecular Pharmacology 44 (2): 346–355. August 1993. doi:10.1016/S0026-895X(25)13176-3. PMID 8394991. 
  • "Structure of the bradykinin B2 receptors' amino terminus". Biochemistry 35 (23): 7514–7519. June 1996. doi:10.1021/bi9601060. PMID 8652530. 
  • "Bradykinin enhances GLUT4 translocation through the increase of insulin receptor tyrosine kinase in primary adipocytes: evidence that bradykinin stimulates the insulin signalling pathway". Diabetologia 39 (4): 412–420. April 1996. doi:10.1007/BF00400672. PMID 8777990. 
  • "Protein kinases A and C rapidly modulate expression of human lung fibroblast B2 bradykinin receptor affinity forms". European Journal of Cell Biology 69 (3): 236–244. March 1996. PMID 8900488. 
  • "Correlations in palmitoylation and multiple phosphorylation of rat bradykinin B2 receptor in Chinese hamster ovary cells". The Journal of Biological Chemistry 274 (13): 8539–8545. March 1999. doi:10.1074/jbc.274.13.8539. PMID 10085087. 
  • "Two B1 and B2 bradykinin receptor antagonists fail to inhibit the Ca2+ response elicited by bradykinin in human skin fibroblasts". General Pharmacology 32 (2): 239–244. February 1999. doi:10.1016/S0306-3623(98)00275-4. PMID 10188626. 
  • "Human chemokine receptors CCR5, CCR3 and CCR2B share common polarity motif in the first extracellular loop with other human G-protein coupled receptors implications for HIV-1 coreceptor function". European Journal of Biochemistry 263 (3): 746–756. August 1999. doi:10.1046/j.1432-1327.1999.00553.x. PMID 10469138. 
  • "Endothelial nitric oxide synthase interactions with G-protein-coupled receptors". The Biochemical Journal 343 Pt 2 (Pt 2): 335–340. October 1999. doi:10.1042/0264-6021:3430335. PMID 10510297. 
  • "Regulation of the human bradykinin B2 receptor expressed in sf21 insect cells: a possible role for tyrosine kinases". Journal of Cellular Biochemistry 76 (4): 658–673. January 2000. doi:10.1002/(SICI)1097-4644(20000315)76:4<658::AID-JCB14>3.0.CO;2-7. PMID 10653985. 
  • "Interaction of endothelial and neuronal nitric-oxide synthases with the bradykinin B2 receptor. Binding of an inhibitory peptide to the oxygenase domain blocks uncoupled NADPH oxidation". The Journal of Biological Chemistry 275 (8): 5291–5296. February 2000. doi:10.1074/jbc.275.8.5291. PMID 10681501. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.




Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Bradykinin_receptor_B2&oldid=4518223"