Nuclear receptor heterodimers recognize response elements composed of
two direct repeats of the consensus sequence 5'-AGGTCA-3' separated by
one to five base pairs. The 1.9 Angstrom crystal structure of the com
plex formed by the DNA-binding domains of the 9-cis retinoic acid rece
ptor and thyroid hormone receptor bound to a thyroid-response element
shows that the subunits interact through a DNA-supported interface inv
olving the carboxy-terminal extension of the DNA-binding domain of the
thyroid hormone receptor. The stereochemistry suggests a mechanism by
which heterodimers recognize the inter-half-site spacing between dire
ct repeats.