A single amino acid residue replacement in the β subunit of human chorionic gonadotrophin results in the loss of biological activity

Chen, F; Puett, David

doi:10.1677/jme.0.0080087

Cited by 15 publications

(3 citation statements)

References 8 publications

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“…Based on results from our laboratory the minimum structural requirements of this region for receptor binding activity seem to be the Cys residue at 93 and 100 and net positive charge. The importance of this region as such, and several critical residues in it, for receptor binding have also been shown using chimeric and mutagenesis approaches by other groups (26–31).…”

Section: Discussionmentioning

confidence: 99%

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its β‐subunit: possible involvement of the disulfide bonds Cys⁹−Cys⁵⁷ and Cys²³−Cys⁷² in receptor binding of the hormone

Mishra

Mahale

Iyer

2001

The Journal of Peptide Research

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Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone essential for the establishment and maintenance of pregnancy. The alpha- and beta-subunits of hCG are highly cross-linked internally by disulfide bonds which seem to stabilize the tertiary structures required for the noncovalent association of the subunits to generate hormonal activity. The purpose of this study was to delineate the role of the disulfide bonds of hCGbeta in receptor binding of the hormone. Six disulfide peptides incorporating each of the six disulfide bonds of hCGbeta were synthesized and screened, along with their linear counterparts, for their ability to competitively inhibit the binding of [125I] hCG to sheep ovarian corpora luteal LH/CG receptor. Disulfide peptide Cys (9-57) was found to be approximately 4-fold more potent than the most active of its linear counterparts in inhibiting radiolabeled hCG from binding to its receptor. Similarly, disulfide peptide Cys (23-72) exhibited receptor binding inhibition activity, whereas the constituent linear peptides were found to be inactive. The results suggest the involvement of the disulfide bonds Cys(9)-Cys(57) and Cys(23)-Cys(72) of the beta-subunit of hCG in receptor binding of the hormone. This study is the first of its kind to use disulfide peptides rather than linear peptides to map the receptor binding regions of hCG.

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Section: Discussionmentioning

confidence: 99%

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its β‐subunit: possible involvement of the disulfide bonds Cys⁹−Cys⁵⁷ and Cys²³−Cys⁷² in receptor binding of the hormone

Mishra

Mahale

Iyer

2001

The Journal of Peptide Research

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“…By homologous modelling, Willey and Leidenberger (1989) suggested that, for hCG, Ser-38 and His-83 on the a-subunit formed a similar active site with the j3-subunit Asp-99, the latter being the only conserved aspartic acid residue in all reported j3-subunit sequences (Bousfield et al, 1987). Recently, Chen and Puett (1992) changed the hCG 13-subunit Asp-99 to an arginine residue by sitedirected mutagenesis.…”

Section: Theoretical Tertiary and Quaternary Modelsmentioning

confidence: 99%

Hormones of the Placenta: hCG and hPL

Butt¹,

Chard²,

Iles³

1994

Marshall’s Physiology of Reproduction

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“…By homolo¬ gous modelling, Willey & Leidenberger (1989) sug¬ gested that, for hCG, Ser38 and His83 on the a-subunit formed a similar active site with the ß-subunit Asp99, this being the only conserved aspartic acid residue of all reported ß-subunit sequences ). Recently, Chen & Puett (1992) changed the hCG ß-subunit Asp99 to an arginine residue by site-directed mutagenesis.…”

Section: Detection and Measurement Of Hcgmentioning

confidence: 99%

Molecular insights into the structure and function of human chorionic gonadotrophin

Iles

Chard²

1993

Journal of Molecular Endocrinology

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Although discovered in the early 1930s, much of the biochemistry and molecular biology of human chorionic gonadotrophin (hCG) has only recently been revealed. The sequence was described in 1973 (Bellisario et al. 1973;Carlsen et al. 1973), but the precise secondary and tertiary structures are still unknown. Only in the last 5 years has there been dramatic progress in the understanding of the molecular nature of this hormone. These studies shed light on many clinical aspects of the biology of hCG, including its association with non\x=req-\ trophoblastic epithelial cancers.CG and the glycoprotein hormones Chorionic gonadotrophin is a member of a group of four structurally homologous proteins commonly referred to as the glycoprotein hormones. As the name implies, the hormone protein chains are glycosylated; hCG contains approximately 30% carbohydrate by weight. The other members are luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH). CG differs from the other glycoprotein hormones in that it is produced by the placenta, whilst LH, FSH and TSH are pituitary products. CG, LH and FSH are gonadotrophins, stimulating ovarian and testicular functions via the regulation of gametogenesis and gonadal steroid hormone synthesis. TSH acts on the thyroid gland resulting in the synthesis and secretion of thyroid hormones. All share a common subunit structure of a-and ß-peptide chains which are noncovalently joined. The a-subunit is common to all members of the family whilst the ß-subunits differ and confer hormonal specificity. The subunits are biologically inactive in the free form; only the a-ß heterodimer is able to bind to and stimulate the hormone receptors (reviewed by Pierce 8c Parsons, 1981). The peptide chains show close homology, the greatest being between the ß-subunits of LH and CG (81%). hCG and LH bind to the same gonadal receptor, stimulating steroid synthesis and luteiniza-

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A single amino acid residue replacement in the β subunit of human chorionic gonadotrophin results in the loss of biological activity

Cited by 15 publications

References 8 publications

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its β‐subunit: possible involvement of the disulfide bonds Cys⁹−Cys⁵⁷ and Cys²³−Cys⁷² in receptor binding of the hormone

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its β‐subunit: possible involvement of the disulfide bonds Cys⁹−Cys⁵⁷ and Cys²³−Cys⁷² in receptor binding of the hormone

Hormones of the Placenta: hCG and hPL

Molecular insights into the structure and function of human chorionic gonadotrophin

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A single amino acid residue replacement in the β subunit of human chorionic gonadotrophin results in the loss of biological activity

Cited by 15 publications

References 8 publications

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its β‐subunit: possible involvement of the disulfide bonds Cys9−Cys57 and Cys23−Cys72 in receptor binding of the hormone

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its β‐subunit: possible involvement of the disulfide bonds Cys9−Cys57 and Cys23−Cys72 in receptor binding of the hormone

Hormones of the Placenta: hCG and hPL

Molecular insights into the structure and function of human chorionic gonadotrophin

Contact Info

Product

Resources

About

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its β‐subunit: possible involvement of the disulfide bonds Cys⁹−Cys⁵⁷ and Cys²³−Cys⁷² in receptor binding of the hormone

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its β‐subunit: possible involvement of the disulfide bonds Cys⁹−Cys⁵⁷ and Cys²³−Cys⁷² in receptor binding of the hormone