A single-chain tetradomain glycoprotein hormone analog elicits multiple hormone activities in vivo

Biology of Reproduction
Vicenta Garcia-CampayoT Rajendra Kumar

Abstract

We previously demonstrated that genetically linking one or more of the glycoprotein hormone-specific beta subunit genes to the common alpha subunit resulted in single-chain analogues that were bioactive in vitro. The ability of such large structures to bind their cognate receptors with high affinity supported the hypothesis that extensive flexibility exists between the ligand and receptor to establish a functional complex. To further characterize the extent of this conformational flexibility, we engineered a single-chain analogue that consists of sequentially linked thyroid-stimulating hormone (TSH) beta, follicle-stimulating hormone (FSH) beta, and chorionic gonadotropin (CG) beta subunits to the alpha subunit and expressed this chimera in transfected CHO (Chinese hamster ovary) cells. Because the four subunits are genetically linked and expressed as a single-chain, this analogue presumably lacks significant native structural features of the individual heterodimers. However, it exhibited FSH, CG, and TSH activities in vitro. Here, we test whether this nonnative structure would be stable in vivo and thus biologically active. Using a variety of bioassay protocols, we demonstrate that the analogue elicits multihormone activities ...Continue Reading

References

Jun 1, 1989·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M R Sairam
Jan 1, 1981·Annual Review of Biochemistry·J G Pierce, T F Parsons
Feb 1, 1995·Thyroid : Official Journal of the American Thyroid Association·J East-PalmerB D Weintraub
Mar 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·T SugaharaI Boime
Jun 1, 1997·Fertility and Sterility·M Filicori
Mar 25, 1998·Human Reproduction·L Andrews, N Elster
Jun 30, 1998·Endocrinology·T R KumarM M Matzuk
Oct 2, 1998·Human Reproduction·K Diedrich, R Felberbaum
Jun 24, 1999·Molecular Endocrinology·J A ElvinM M Matzuk
Feb 13, 2001·Trends in Endocrinology and Metabolism : TEM·V Garcia-Campayo, I Boime
Apr 18, 2001·Reproduction in Domestic Animals = Zuchthygiene·R Cortvrindt, J Smitz
Dec 12, 2002·The Journal of Endocrinology·P J O'Shea, G R Williams
Dec 25, 2002·Human Reproduction Update·Marco FilicoriDomenico DeAloysio
Apr 4, 2003·Biology of Reproduction·Martin M MatzukT Rajendra Kumar

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Citations

Aug 27, 2005·Reproduction : the Official Journal of the Society for the Study of Fertility·T Rajendra Kumar
Apr 29, 2006·Molecular and Cellular Endocrinology·Ruth Braw-TalDavid Ben-Menahem
Mar 27, 2018·Endocrinology·T Rajendra Kumar
Jul 9, 2016·Molecular Endocrinology·Gunnar KleinauAnnette Grüters-Kieslich
May 7, 2013·Endocrine Reviews·Gunnar KleinauHeike Biebermann

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Methods Mentioned

BETA
glycosylation
PCR
gene knockout

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SeqWright
Adobe Photoshop
Excel

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