Corticosteroid-binding globulin

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 7: Line 7:
==Introduction==
==Introduction==
-
Corticosteroid-binding globulin (CBG) is a blood plasma protein 50 to 60 kDa in size <ref>PMID:13395526 </ref>,<ref>PMID:7074030 </ref>. Although it is a member of the serine protease inhibitor (SERPIN) structural family, it does not have any known intrinsic serine protease inhibitor activity <ref>PMID:3143075 </ref>. Its physiological function is conventionally thought to be the transport of the weakly water-soluble hormone, cortisol, throughout the circulation <ref>PMID:13395526 </ref>,<ref>PMID:7074030 </ref>. Structural studies of native rat CBG <ref>PMID:17644521 </ref> and a cleaved human CBG-antitrypsin chimera <ref>PMID:18513745 </ref> have corroborated earlier biochemical studies showing that cortisol binds to CBG with a one-to-one stoichiometry. Additionally, CBG is believed to buffer the concentration of free cortisol in the blood, keeping the level constant despite its pulsatile secretion pattern.
+
Corticosteroid-binding globulin (CBG) is a blood plasma protein 50 to 60 kDa in size <ref>PMID:13395526 </ref>,<ref>PMID:7074030 </ref>. Although it is a member of the serine protease inhibitor (SERPIN) structural family, it does not have any known intrinsic serine protease inhibitor activity <ref>PMID:3143075 </ref>. Its physiological function is conventionally thought to be the transport of the weakly water-soluble hormone, cortisol, throughout the circulation <ref>PMID:13395526 </ref>,<ref>PMID:7074030 </ref>. Structural studies of native rat CBG <ref>PMID:17644521 </ref> and a cleaved human CBG-antitrypsin chimera <ref>PMID:18513745 </ref> have corroborated earlier biochemical studies showing that cortisol binds to CBG with a one-to-one stoichiometry. Additionally, CBG is believed to buffer the concentration of free cortisol in the blood, keeping the level constant despite its pulsatile secretion pattern <ref>PMID:9751481 </ref>. CBG is also thought to participate in the stress response by releasing cortisol specifically at inflammatory sites upon cleavage by human neutrophil elastase between residues 344 and 345<ref>PMID:3143075 </ref>.
 +
 
 +
==Gene==
 +
 
 +
The gene encoding corticosteroid-binding globulin is located at the 370kb long chromosome locus 14q32.1 among ten other related genes and pseudogenes. The transcriptional activation of this gene cluster appears to be coordinately regulated by a locus control region upstream of the alpha-1-anti-trypsin gene that responds to transcription factors such as hepatic nuclear factors HNF-1 and -4<ref>PMID:17547679 </ref>,<ref>PMID:19643161 </ref>.

Revision as of 20:43, 7 June 2012


Introduction

Corticosteroid-binding globulin (CBG) is a blood plasma protein 50 to 60 kDa in size [1],[2]. Although it is a member of the serine protease inhibitor (SERPIN) structural family, it does not have any known intrinsic serine protease inhibitor activity [3]. Its physiological function is conventionally thought to be the transport of the weakly water-soluble hormone, cortisol, throughout the circulation [4],[5]. Structural studies of native rat CBG [6] and a cleaved human CBG-antitrypsin chimera [7] have corroborated earlier biochemical studies showing that cortisol binds to CBG with a one-to-one stoichiometry. Additionally, CBG is believed to buffer the concentration of free cortisol in the blood, keeping the level constant despite its pulsatile secretion pattern [8]. CBG is also thought to participate in the stress response by releasing cortisol specifically at inflammatory sites upon cleavage by human neutrophil elastase between residues 344 and 345[9].

Gene

The gene encoding corticosteroid-binding globulin is located at the 370kb long chromosome locus 14q32.1 among ten other related genes and pseudogenes. The transcriptional activation of this gene cluster appears to be coordinately regulated by a locus control region upstream of the alpha-1-anti-trypsin gene that responds to transcription factors such as hepatic nuclear factors HNF-1 and -4[10],[11].



References

  1. ↑ WESTPHAL U. Steroid-protein interactions. III. Spectrophotometric demonstration of interaction between proteins and progesterone, deoxycorticosterone and cortisol. Arch Biochem Biophys. 1957 Jan;66(1):71-90. PMID:13395526
  2. ↑ Mickelson KE, Harding GB, Forsthoefel M, Westphal U. Steroid-protein interactions. Human corticosteroid-binding globulin: characterization of dimer and electrophoretic variants. Biochemistry. 1982 Feb 16;21(4):654-60. PMID:7074030
  3. ↑ Pemberton PA, Stein PE, Pepys MB, Potter JM, Carrell RW. Hormone binding globulins undergo serpin conformational change in inflammation. Nature. 1988 Nov 17;336(6196):257-8. PMID:3143075 doi:http://dx.doi.org/10.1038/336257a0
  4. ↑ WESTPHAL U. Steroid-protein interactions. III. Spectrophotometric demonstration of interaction between proteins and progesterone, deoxycorticosterone and cortisol. Arch Biochem Biophys. 1957 Jan;66(1):71-90. PMID:13395526
  5. ↑ Mickelson KE, Harding GB, Forsthoefel M, Westphal U. Steroid-protein interactions. Human corticosteroid-binding globulin: characterization of dimer and electrophoretic variants. Biochemistry. 1982 Feb 16;21(4):654-60. PMID:7074030
  6. ↑ Klieber MA, Underhill C, Hammond GL, Muller YA. Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release. J Biol Chem. 2007 Oct 5;282(40):29594-603. Epub 2007 Jul 19. PMID:17644521 doi:10.1074/jbc.M705014200
  7. ↑ Zhou A, Wei Z, Stanley PL, Read RJ, Stein PE, Carrell RW. The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release. J Mol Biol. 2008 Jun 27;380(1):244-51. Epub 2008 May 14. PMID:18513745 doi:10.1016/j.jmb.2008.05.012
  8. ↑ Windle RJ, Wood SA, Lightman SL, Ingram CD. The pulsatile characteristics of hypothalamo-pituitary-adrenal activity in female Lewis and Fischer 344 rats and its relationship to differential stress responses. Endocrinology. 1998 Oct;139(10):4044-52. PMID:9751481
  9. ↑ Pemberton PA, Stein PE, Pepys MB, Potter JM, Carrell RW. Hormone binding globulins undergo serpin conformational change in inflammation. Nature. 1988 Nov 17;336(6196):257-8. PMID:3143075 doi:http://dx.doi.org/10.1038/336257a0
  10. ↑ Torpy DJ, Ho JT. Corticosteroid-binding globulin gene polymorphisms: clinical implications and links to idiopathic chronic fatigue disorders. Clin Endocrinol (Oxf). 2007 Aug;67(2):161-7. Epub 2007 Jun 4. PMID:17547679 doi:10.1111/j.1365-2265.2007.02890.x
  11. ↑ Lin HY, Muller YA, Hammond GL. Molecular and structural basis of steroid hormone binding and release from corticosteroid-binding globulin. Mol Cell Endocrinol. 2010 Mar 5;316(1):3-12. Epub 2009 Jul 28. PMID:19643161 doi:10.1016/j.mce.2009.06.015

Proteopedia Page Contributors and Editors (what is this?)

Wee Lee Chan, Michal Harel, Alexander Berchansky

Retrieved from "http://52.214.119.220/wiki/index.php/Corticosteroid-binding_globulin"
Personal tools