| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Molecular Biology and Pharmacology (A.M.J.,
M.P., I.B.) Washington University School of Medicine St
Louis, Missouri 63110
Institute for Biomedical Aging Research
(P.B.) Austrian Academy of Sciences A-6020 Innsbruck,
Austria
Division of Reproductive Biology (C.K., A.W.J.H.)
Department of Gynecology/Obstetrics Stanford University Medical
Center Stanford, California 94305
Human CG (hCG) is a member of the glycoprotein
hormone family characterized by a heterodimeric structure consisting of
a common 
-subunit noncovalently bound to a hormone-specific
ß-subunit. The two subunits are highly intertwined and only the
heterodimer is functional, implying that the quaternary structure is
critical for biological activity. To assess the dependence of the
bioactivity of hCG on the heterodimeric interactions, - and
ß-subunits bearing mutations that prevent assembly were covalently
linked to form a single chain hCG. Receptor binding and signal
transduction of these analogs were tested and their structural
integrity analyzed using a panel of monoclonal antibodies (mAbs). These
included dimer-specific mAbs, which react with at least four different
epitope sites on the hormone, and some that react only with the free
ß-subunit. We showed that there was significant loss of quaternary
and tertiary structure in several regions of the molecule. This was
most pronounced in single chains that had one of the disulfide bonds of
the cystine knot disrupted in either the - or ß-subunit. Despite
these structural changes, the in vitro receptor binding and
signal transduction of the single chain analogs were comparable to
those of the nonmutated single chain, demonstrating that not all of the
quaternary configuration of the hormone is necessary for biological
activity.
This article has been cited by other articles:
 |
|
 |
|
  A. Jablonka-Shariff, T. R. Kumar, J. Eklund, A. Comstock, and I. Boime Single-Chain, Triple-Domain Gonadotropin Analogs with Disulfide Bond Mutations in the {alpha}-Subunit Elicit Dual Follitropin and Lutropin Activities in Vivo Mol. Endocrinol., June 1, 2006; 20(6): 1437 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Garcia-Campayo, I. Boime, X. Ma, D. Daphna-Iken, and T. R. Kumar A Single-Chain Tetradomain Glycoprotein Hormone Analog Elicits Multiple Hormone Activities In Vivo Biol Reprod, February 1, 2005; 72(2): 301 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Garcia-Campayo, A. Jablonka-Shariff, and I. Boime A Single-chain Bifunctional Gonadotropin Analog Is Secreted from Chinese Hamster Ovary Cells as Two Distinct Bioactive Species J. Biol. Chem., October 22, 2004; 279(43): 44286 - 44293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sohn, H. Youn, M. Jeoung, Y. Koo, C. Yi, I. Ji, and T. H. Ji Orientation of Follicle-stimulating Hormone (FSH) Subunits Complexed with the FSH Receptor: {beta} SUBUNIT TOWARD THE N TERMINUS OF EXODOMAIN AND {alpha} SUBUNIT TO EXOLOOP 3 J. Biol. Chem., November 28, 2003; 278(48): 47868 - 47876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Fralish, B. Dattilo, and D. Puett Structural Analysis of Yoked Chorionic Gonadotropin-Luteinizing Hormone Receptor Ectodomain Complexes by Circular Dichroic Spectroscopy Mol. Endocrinol., July 1, 2003; 17(7): 1192 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Fralish, P. Narayan, and D. Puett Consequences of Single-Chain Translation on the Structures of Two Chorionic Gonadotropin Yoked Analogs in {alpha}-{beta} and {beta}-{alpha} Configurations Mol. Endocrinol., April 1, 2003; 17(4): 757 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Narayan, J. Gray, and D. Puett Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Garcia-Campayo, T. R. Kumar, and I. Boime Thyrotropin, Follitropin, and Chorionic Gonadotropin Expressed as a Single Multifunctional Unit Reveal Remarkable Permissiveness in Receptor-Ligand Interactions Endocrinology, October 1, 2002; 143(10): 3773 - 3778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xing, W. Lin, M. Jiang, R. V. Myers, D. Cao, M. P. Bernard, and W. R. Moyle Alternatively Folded Choriogonadotropin Analogs. IMPLICATIONS FOR HORMONE FOLDING AND BIOLOGICAL ACTIVITY J. Biol. Chem., December 7, 2001; 276(50): 46953 - 46960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Garcia-Campayo and I. Boime Independent Activities of FSH and LH Structurally Confined in a Single Polypeptide: Selective Modification of the Relative Potencies of the Hormones Endocrinology, December 1, 2001; 142(12): 5203 - 5211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hiro'oka, D. Maassen, P. Berger, and I. Boime Disulfide Bond Mutations in Follicle-Stimulating Hormone Result in Uncoupling of Biological Activity from Intracellular Behavior Endocrinology, December 1, 2000; 141(12): 4751 - 4756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Darling, J. A. Wilken, A. K. Miller-Lindholm, T. M. Urlacher, R. W. Ruddon, S. A. Sherman, and E. Bedows Functional Contributions of Noncysteine Residues within the Cystine Knots of Human Chorionic Gonadotropin Subunits J. Biol. Chem., March 30, 2001; 276(14): 10692 - 10699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ben-Menahem, A. Jablonka-Shariff, R. K. Hyde, M. R. Pixley, S. Srivastava, P. Berger, and I. Boime The Position of the alpha and beta Subunits in a Single Chain Variant of Human Chorionic Gonadotropin Affects the Heterodimeric Interaction of the Subunits and Receptor-binding Epitopes J. Biol. Chem., August 3, 2001; 276(32): 29871 - 29879. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
