Disulfide bonds Cys(9)-Cys(57), Cys(34)-Cys(88) and Cys(38)-Cys(90) of the beta-subunit of human chorionic gonadotropin are crucial for heterodimer formation with the alpha-subunit: experimental evidence for the conclusions from the crystal structure of hCG.
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 that seem to stabilize the tertiary structures required for the noncovalent association of the subunits to generate hormonal activity. This paper describes the results of our studies on the role of the disulfide bonds of hCG-beta in heterodimer formation with the alpha-subunit. Six disulfide peptides incorporating each of the six disulfide bonds of hCG-beta were screened, along with their linear counterparts, for their ability to competitively inhibit the recombination of alpha- and beta-subunits. The disulfide peptides Cys (9-57), Cys (34-88) and Cys (38-90) were found to inhibit the alpha/beta recombination whereas the remaining three disulfide peptides viz. Cys (23-72), Cys (26-110) and Cys (93-100) did not exhibit any inhibition activity. Interestingly, none of the linear peptides could inhibit the alpha/beta recombination. Results clearly demonstrate that the disulfide bonds Cys(9)-Cys(57), Cys(34)-Cys(88) and Cys(38)-Cys(90) of the beta-subunit of hCG are crucial for heterodimer formation with the alpha-subunit thus providing experimental confirmation of the conclusions from the crystal structure of the hormone.
Mishra
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AK
Biotech Two, Suite 115, Molecular Medicine, University of Massachusetts Medical School (UMASS), 373 Plantation Street, Worcester, MA 01605, USA.
Mahale
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Iyer
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KS
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry*; D003460:Crystallization; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry*; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis; D011995:Recombination, Genetic
D018997:Chorionic Gonadotropin, beta Subunit, Human; D004220:Disulfides; D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments