title: Structural basis for nuclear hormone receptor DNA binding.
abstract: The gene family of nuclear receptors is characterized by the presence of a typical, well conserved DNA-binding domain. In general, two zinc coordinating modules are folded such that an α-helix is inserted in the major groove of the DNA-helix displaying a sequence similar to one of two hexameric consensus motifs. Both zinc molecules coordinate four cysteines. Although the DNA-binding domains as well as the hormone response elements are very similar, each nuclear receptor will affect transcription of a specific set of target genes. This is in part due to some important receptor-specific variations on the general theme of DNA interaction. For most nuclear receptors, the DNA-binding domain dimerizes on DNA, which explains why most hormone response elements consist of a repeat of two hexamers. The hexamer dimers can be organized either as direct, inverted or everted repeats with spacers of varying lengths. The DNA can be bound by homodimers, heterodimers and for some orphan receptors, as monomer. Another key element for DNA binding by nuclear receptors is the carboxy-terminal extension of the DNA-binding domain extending into the hinge region. This part not only co-determines sequence specificity, but also affects other functions of the receptors like nuclear translocation, intranuclear mobility and transactivation potential. Moreover, allosteric signals passing through towards other receptor domains, explain why to some extent, the DNA elements can also be considered as controlling ligands.
authors.affiliation: Molecular Endocrinology Laboratory, Department Molecular Cell Biology, Campus GHB, ON1, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Helsen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kerkhofs
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Clinckemalie
authors.forename: Lien
authors.initials: L
authors.lastname: Spans
authors.forename: Michaël
authors.initials: M
authors.lastname: Laurent
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.forename: Frank
authors.initials: F
authors.lastname: Claessens
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D020218:Response Elements; D015533:Transcriptional Activation
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D004247:DNA