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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sugahara, T. Hsueh, A. J. Ben-menahem, D. Boime, I. Perlas, E. Minami, S. Pixley, M. R. |
| Description | Author Affiliation: Sugahara T ( Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.); |
| Abstract | One of the distinguishing features of the gonadotropin and thyrotropin hormone family is their heterodimeric structure, consisting of a common alpha subunit and a hormone-specific beta subunit. Subunit assembly is vital to the function of these hormones: The conformation of the heterodimer is essential for controlling secretion, hormone-specific posttranslational modifications, and signal transduction. To address whether alpha and beta subunits can be synthesized as one chain and also maintain biological activity, a chimera composed of the human chorionic gonadotropin (hCG) beta subunit genetically fused to the alpha subunit was constructed. The resulting polypeptide hCG molecule not only was efficiently secreted but also displayed an increased biological activity in vitro and in vivo. These data show that the alpha and hCG beta subunits encoded as a single chain retain a biologically active conformation similar to that seen in the heterodimer. This approach can be used to investigate structure-function relationships of the glycoprotein hormone family that were previously not tractable because of the absolute dependence on assembly for the biological response. Moreover, other bioactive multisubunit ligands can be engineered where the combination efficiency and specificity of heterodimers and homodimers are otherwise difficult to control. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 92 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1995-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Chorionic Gonadotropin Biosynthesis Chemistry Recombinant Proteins Animals Biological Assay CHO Cells Pharmacology Cricetinae DNA Primers Dose-Response Relationship, Drug Exons Follicle Stimulating Hormone Macromolecular Substances Molecular Sequence Data Mutagenesis Ovarian Follicle Drug Effects Physiology Ovulation Polymerase Chain Reaction Transfection Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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