HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vivat, V Articles by Gronemeyer, H Search for Related Content PubMed PubMed Citation Articles by Vivat, V Articles by Gronemeyer, H

The natural ligands of the progesterone (PR) and androgen (AR) receptors, progesterone and testosterone, differ only by their 17β-substitution. To identify within the AR and PR ligand-binding domains (LBDs) the sequences responsible for the differential recognition of these ligands, chimeric LBDs assembled from five homologous AR/PR 'cassettes' linked to the GAL4-DNA binding domain were constructed, and their ligand binding and transactivation characteristics were determined. Replacing the central cassette 3 of PR by that of AR generated a progesterone- and testosterone-responsive PR LBD with the AR residues 788-RHLS-791 being specifically involved in testosterone recognition, while the introduction of the C-terminal PR cassette 5 into AR conferred progestin responsiveness onto the AR LBD. These results suggest that residues within AR 788-RHLS-791 interact with the testosterone 17β-OH, while PR cassette 5 apparently contains the amino acid(s) specifically involved in the recognition of the progesterone 17β-acetyl group. However, ligand binding and transactivation by these chimeras were significantly decreased compared with those of the parental LBDs, indicating that residues located outside of these cassettes contribute to the proper positioning of the steroids in the AR and PR ligand-binding pockets (LBPs). Indeed, certain AR/PR chimeras acquired efficient ligand binding, but were unable to transactivate, indicating that the ligand was improperly bound in the chimeric LBP and could not induce the conformational changes leading to a transcriptionally competent activation function (AF-2) within the LBD. The properties of the various LBD chimeras are discussed in view of the recently solved three-dimensional structures of the retinoid X receptor apo- and retinoic acid receptor holo-LBDs.

This article has been cited by other articles:

				J. B Pippal and P. J Fuller Structure-function relationships in the mineralocorticoid receptor J. Mol. Endocrinol., December 1, 2008; 41(6): 405 - 413. [Abstract] [Full Text] [PDF]

				F. M. Rogerson, Y.-Z. Yao, R. E. Elsass, N. Dimopoulos, B. J. Smith, and P. J. Fuller A Critical Region in the Mineralocorticoid Receptor for Aldosterone Binding and Activation by Cortisol: Evidence for a Common Mechanism Governing Ligand Binding Specificity in Steroid Hormone Receptors Mol. Endocrinol., April 1, 2007; 21(4): 817 - 828. [Abstract] [Full Text] [PDF]

				J. Zhang, J. Simisky, F. T. F. Tsai, and D. S. Geller A critical role of helix 3-helix 5 interaction in steroid hormone receptor function PNAS, February 22, 2005; 102(8): 2707 - 2712. [Abstract] [Full Text] [PDF]

				Q. Wang, T. S. Udayakumar, T. S. Vasaitis, A. M. Brodie, and J. D. Fondell Mechanistic Relationship between Androgen Receptor Polyglutamine Tract Truncation and Androgen-dependent Transcriptional Hyperactivity in Prostate Cancer Cells J. Biol. Chem., April 23, 2004; 279(17): 17319 - 17328. [Abstract] [Full Text] [PDF]

				J. Sun, J. Baudry, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Molecular Basis for the Subtype Discrimination of the Estrogen Receptor-{beta}-Selective Ligand, Diarylpropionitrile Mol. Endocrinol., February 1, 2003; 17(2): 247 - 258. [Abstract] [Full Text] [PDF]

				C. Robin-Jagerschmidt, J.-M. Wurtz, B. Guillot, D. Gofflo, B. Benhamou, A. Vergezac, C. Ossart, D. Moras, and D. Philibert Residues in the Ligand Binding Domain That Confer Progestin or Glucocorticoid Specificity and Modulate the Receptor Transactivation Capacity Mol. Endocrinol., July 1, 2000; 14(7): 1028 - 1037. [Abstract] [Full Text]

				F. M. Rogerson, N. Dimopoulos, P. Sluka, S. Chu, A. J. Curtis, and P. J. Fuller Structural Determinants of Aldosterone Binding Selectivity in the Mineralocorticoid Receptor J. Biol. Chem., December 17, 1999; 274(51): 36305 - 36311. [Abstract] [Full Text] [PDF]

				K. Ekena, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Determinants of Ligand Specificity of Estrogen Receptor-alpha : Estrogen versus Androgen Discrimination J. Biol. Chem., January 9, 1998; 273(2): 693 - 699. [Abstract] [Full Text] [PDF]