Vol 64, No 4 (2013)
Review paper
Submitted: 2013-09-04
Accepted: 2013-09-04
Published online: 2013-09-04
Significance of the disulphide bonds of human growth hormone
Riia K. Junnila, John J. Kopchick
DOI: 10.5603/EP.2013.0009
·
Endokrynol Pol 2013;64(4):300-305.
Vol 64, No 4 (2013)
Review Article
Submitted: 2013-09-04
Accepted: 2013-09-04
Published online: 2013-09-04
Abstract
Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene,have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH.In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despitedecreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study.To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders.
Abstract
Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene,have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH.In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despitedecreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study.To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders.
Keywords
growth hormone, disulphides, structure-activity relationship
Title
Significance of the disulphide bonds of human growth hormone
Journal
Endokrynologia Polska
Issue
Vol 64, No 4 (2013)
Article type
Review paper
Pages
300-305
Published online
2013-09-04
Page views
1662
Article views/downloads
3218
DOI
10.5603/EP.2013.0009
Bibliographic record
Endokrynol Pol 2013;64(4):300-305.
Keywords
growth hormone
disulphides
structure-activity relationship
Authors
Riia K. Junnila
John J. Kopchick
About this article
