The invention provides chimeric proteins having at least two functional
protein units, each containing the dimerization domain of a member of the
steroid/thyroid hormone nuclear receptor superfamily. The chimeric
proteins can fold under crystallization conditions to form functional
entities. The functional entities optionally contain a novel flexible
peptide linker of variable lengths between at least two of the protein
units. In a preferred embodiment, the linker is designed to be increased
in increments of 12 amino acids each to aid in preparation of variant
chimeric proteins. The DNA binding characteristics of the invention
functional entities differ from those of wild-type complexes formed
between "monomeric" receptors and their binding partners. Some functional
entities, e.g. dimers expressed as fusion proteins, transactivate
responsive promoters in a manner similar to wild-type complexes, while
others do not promote transactivation and function instead essentially as
constitutive repressors. The invention further provides nucleotide
sequences encoding the invention chimeric proteins, cells containing such
nucleotide sequences, and methods for using the invention chimeric
proteins to modulate expression of one or more exogenous genes in a
subject organism. In addition, isolated protein crystals suitable for
x-ray diffraction analysis and methods for obtaining putative ligands for
the invention chimeric proteins are provided.