Direct evidence for the localization of the steroid-binding site of the plasma sex steroid-binding protein (SBP or SHBG) at the interface between the subunits

Protein Science : a Publication of the Protein Society
L SuiP H Petra

Abstract

Complete dissociation of dimeric plasma sex steroid-binding protein (SBP or SHBG) was obtained in 6 M urea at 10 degrees C. Removal of urea resulted in the refolding of monomers, followed by reformation of dimeric SBP, which migrates with the same mobility as the native protein. Dimerization does not require Ca+2 or steroid. Renatured monomers yield dimers with dissociation constants for 5 alpha-dihydrotesterone (DHT) and 17 beta-estradiol (E2) indistinguishable from those of native human SBP. This phenomenon was also demonstrated by mixing human and rabbit SBPs that, upon renaturation, form a hybrid dimer composed of one human subunit and one rabbit subunit. The hybrid binds both DHT and E2 in contrast to rSBP, which only binds the androgen. Therefore, we conclude that (1) docking of the two subunits creates an asymmetric steroid-binding site located at the interface between the subunits, and (2) only one face of the dimer defines the specificity for binding E2 by encompassing portion of a structural motif that recognizes the flat ring A of E2. The remaining portion, which recognizes the saturated ring A of DHT, is shared by both faces of the dimer. Because native monomers do not exist alone, the often-asked question of whethe...Continue Reading

References

Oct 1, 1978·Journal of Steroid Biochemistry·T TabeiP H Petra
Nov 14, 1978·Biochemical and Biophysical Research Communications·S BordinP H Petra
Jan 1, 1991·The Journal of Steroid Biochemistry and Molecular Biology·W RosnerN A Romas
Jan 1, 1986·Journal of Steroid Biochemistry·P H PetraK Titani
Apr 16, 1985·Biochemical and Biophysical Research Communications·D J HrybW Rosner
Oct 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·S Bordin, P H Petra
Jun 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·A Gerard

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Citations

Feb 28, 2001·The Journal of Steroid Biochemistry and Molecular Biology·P H PétraL M Sui
Aug 29, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Geoffrey L HammondYves A Muller
Mar 8, 2013·Journal of Environmental Radioactivity·Gennady N FilchenkovAlexander D Naumov
Jan 13, 2017·European Journal of Endocrinology·María Del Mar GrasaMarià Alemany
Sep 14, 2017·Endocrine Reviews·David J Handelsman

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