Steroid binding domain

The site-directed photoaffinity ligand [3H]17 beta-hydroxy-4,6-androstadien-3-one (delta 6-testosterone) was used to label the steroid binding domain of rat androgen-binding protein (rABP). After digestion with trypsin, the major radiolabeled peptide was isolated by reverse phase chromatography. The peptide was found to have the following amino acid sequence: Ile Ala Leu Gly Gly Leu Leu Leu Pro Thr Ser. Gaps in the sequence that one would anticipate if delta 6-testosterone formed an adduct with a single amino acid were not encountered. Several different amino acids appear to have been labeled as expected given the free radical nature of photoactivated delta 6-testosterone. The sequence obtained corresponded to a tryptic peptide (amino acids 171-181) of the rABP precursor. The only other protein having this amino acid sequence was human sex hormone binding globulin. The binding domain lies in a hydrophobic pocket that contains a predicted beta-sheet and turn secondary structure, as would be anticipated given the hydrophobic nature of the steroid molecule. A hydropathy and secondary structure analysis of rABP was performed as a basis for discussing the results of the current study in relation to previous studies on the steroid binding domain on human sex hormone binding globulin.

Sex hormone-binding globulin (SHBG) is thought to mainly function as a transporter and reservoir for the estradiol and testosterone sex hormones. However it has also been demonstrated that SHBG can bind to a cell surface receptor (SHBG-R). The SHBG-R has not been completely characterized. A subset of steroids are able to bind to the SHBG/SHBG-R complex resulting in an activation of adenylyl cyclase and synthesis of the cAMP second messenger. [19] Hence the SHBG/SHBG-R complex appears to act as a transmembrane steroid receptor that is capable of transmitting signals to the interior of cells.

Steroid binding domain

steroid binding domain


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