We present findings of genetic information conservation between the glucocorticoid response element (GRE) DNA and the cDNA encoding the glucocorticoid receptor (GR) DNA-binding domain (DBD). The regions of nucleotide sub-sequence similarity to the GRE in the GR DBD occur specifically at nucleotide sequences on the ends of exons 3, 4, and 5 at their splice junction sites. These sequences encode the DNA recognition helix on exon 3, a (3strand on exon 4, and a putative a-helix on exon 5, respectively. The nucleotide sequence of exon 5 that encodes the putative a-helix located on the carboxyl terminus of the GR DBD shares sequence similarity with the flanking nucleotide regions of the GRE. We generated a computer model of the GR DBD using atomic coordinates derived from nuclear magnetic resonance spectroscopy to which we attached the exon 5-encoded putative a-helix. We docked this GR DBD structure at the 39-base-pair nucleotide sequence containing the GRE binding site and flanking nucleotides, which contained conserved genetic information. We observed that amino acids of the DNA recognition helix, the 13-strand, and the putative a-helix are spatially aligned with trinucleotides identical to their cognate codons within the GRE and its flanking nucleotides.The glucocorticoid receptor (GR) DNA-binding domain (DBD) has been well characterized and consists of 150 amino acids that have been shown to be biologically active in vitro (1). We reported earlier that a nucleotide sequence within the cDNA encoding the GR DBD shared a high degree of sub-sequence similarity with a well-characterized glucocorticoid response element (GRE) from mouse mammary tumor virus (MMTV) 5' long terminal repeat. This GR DBD cDNA sub-sequence encoded a predicted a-helix structure on the carboxyl flank of the first zinc finger that we proposed as a putative DNA-recognition helix (2). Recently, our prediction of the GR DNA-recognition a-helix amino acid sequence, its location within the GR DBD, and its orientation toward the DNA within the GRE major-groove half-sites was confirmed by NMR (3) and x-ray crystallography (4).The genomic structure of the human GR gene was recently determined (5); the two zinc fingers of the DBD are separately encoded by 2 of the 10 exons-namely, exons 3 and 4. The DNA-recognition helix encoded in exon 3 is located at the carboxyl terminus of the first zinc finger. Adjacent to the DNA-recognition helix is a structure that has been determined by NMR (3) and x-ray crystallography (4) to be a (3-strand. This (3strand encoded in exon 4 is located on the amino terminus ofthe second zinc finger at the splicejunction site of exons 3 and 4. This splice site occurs at a conserved glycine residue within the steroid receptor family that connects the GR DNA-binding recognition helix and /3-strand structures as a bridge that joins the two zinc fingers. TheThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C....
