Structure of the RXR-RAR DNA-binding complex on the retinoic acid responseelement DR1

The 9-cis retinoic acid receptor (retinoid X receptor, RXR) forms heterodim ers with the all-ti ails retinoic acid receptor (RAR) and other nuclear rec eptors on DNA regulatory sites composed of tandem binding elements. We desc ribe the 1.70 Angstrom resolution structure of the ternary complex of RXR a nd RAR DNA-binding regions in complex with the retinoic acid response eleme nt DR1. The receptors recognize identical half-sites through extensive base -specific contacts; however, RXR binds exclusively to the 3' site to form a n asymmetric complex with the reverse polarity of other RXR heterodimers, T he subunits associate in a strictly DNA-dependent manner using the T-box of RXR and the Zn-II region of RAR, both of which are reshaped in forming the complex, The protein-DNA contacts, the dimerization interface and the DNA curvature in the RSR-RAR complex are distinct from those of the RXR homodim er, which also binds DR1, Together, these structures illustrate ho vv the n uclear receptor superfamily exploits conformational flexibility and locally induced structures to generate combinatorial transcription factors.