STRUCTURAL ELEMENTS OF AN ORPHAN NUCLEAR RECEPTOR-DNA COMPLEX

The nuclear hormone receptors form the largest known family of transcr iption factors. The current notion of receptor DNA discrimination, bas ed solely on one major type of hexameric half-site and a highly conser ved be-residue core DNA-binding domain (DBD), does not adequately desc ribe how more than 150 nonsteroid receptors differentiate among respon se elements. Here, we describe the 2.3 Angstrom crystal structure of t he DNA-binding region of the orphan receptor RevErb arranged as a tand em homodimer on its optimal response element. The structure reveals th e presence of a second major protein-DNA interface adjacent to the cla ssical one involving the half-sites. A sequence comparison of orphan r eceptors suggests that unique minor-groove interactions involving the receptor hinge regions impart the necessary DNA and dimerization speci ficity.