Journal of Molecular Endocrinology

The basis for DNA recognition. (A) The core DBD is the 66-residue region with two zinc-binding modules. This domain is responsible for the recognition of hexameric DNA half sites. Shown on the left are the core DBD structures of RXR (blue) and RAR (red) superimposed. The C-terminal extension (CTE) of the DBD, which lies within the immediate hinge region, can also participate in DNA binding and spacer recognition. Shown on the right is the superposition of the DBD-CTE segments of NGFI-B (green), LRH-1 (cyan), VDR (yellow), TR (magenta), and Rev-Erb (salmon). While the core DBDs are well conserved in folding, the CTE sequences and their structures are divergent. The CTEs can act as discriminators of DNA spacing. (B) RAR DBD interactions with AGGTCA elements. DNA half-site recognition by NRs involves a series of hydrophilic residues positioned on the same face of the DBD recognition helix. These residues read the DNA base pair sequence at the major groove. Other basic amino acids additionally stabilize DNA binding by interacting with the phosphate backbone of the DNA. Crystallographic studies have shown that water molecules (shown as red or black circles) often help mediate DNA contacts.