Conservation of genetic information: a code for site-specific DNA recognition.
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 beta-strand on exon 4, and a putative alpha-helix on exon 5, respectively. The nucleotide sequence of exon 5 that encodes the putative alpha-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 alpha-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 beta-strand, and the putative alpha-helix are spatially aligned with trinucleotides identical to their cognate codons within the GRE and its flanking nucleotides.
Harris
L F
LF
Abbott Northwestern Hospital Cancer Research Laboratory, Minneapolis, MN 55407-3799.
Sullivan
M R
MR
Hickok
D F
DF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003198:Computer Simulation; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D016208:Databases, Factual; D005091:Exons; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism; D011980:Receptors, Progesterone / Q000737:chemistry / Q000378:metabolism
D004268:DNA-Binding Proteins; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D004247:DNA