THE CRYSTAL-STRUCTURE OF THE ESTROGEN-RECEPTOR DNA-BINDING DOMAIN BOUND TO DNA - HOW RECEPTORS DISCRIMINATE BETWEEN THEIR RESPONSE ELEMENTS

The nuclear hormone receptors are a superfamily of ligand-activated DN A-binding transcription factors. We have determined the crystal struct ure (at 2.4 angstrom) of the fully specific complex between the DNA-bi nding domain from the estrogen receptor and DNA. The protein binds as a symmetrical dimer to its palindromic binding site consisting of two 6 bp consensus half sites with three intervening base pairs. This stru cture reveals how the protein recognizes its own half site sequence ra ther than that of the related glucocorticoid receptor, which differs b y only two base pairs. Since all nuclear hormone receptors recognize o ne or the other of these two consensus half site sequences, this recog nition mechanism applies generally to the whole receptor family.