title: DNA recognition by the oestrogen receptor: from solution to the crystal.
abstract: BACKGROUND
  The steroid/nuclear hormone receptors are a large family of conserved ligand-activated transcription factors that regulate gene expression through binding to response elements upstream of their target genes. Most members of this family bind to DNA as homodimers or heterodimers and recognize the sequence, spacing and orientation of the two half-sites of their response elements. The recognition and discrimination of the sequence and arrangements of these half-sites are mediated primarily by a highly conserved DNA-binding domain.
  
  
  RESULTS
  Here we describe the DNA-binding properties of the isolated DNA-binding domain of the oestrogen receptor, the ERDBD, and its refined NMR structure. This domain is monomeric in solution, but two molecules bind cooperatively to specific DNA sequences; this cooperativity determines the arrangement of half-sites that is recognized by the ERDBD. The 10 carboxy-terminal residues and a region of 15 residues within the domain are disordered in the solution structure, yet are important for DNA binding.
  
  
  CONCLUSIONS
  The cooperative nature of ERDBD binding to DNA is important. The previously-determined X-ray structure of the ERDBD dimer bound to DNA shows that the 15 internal residues disordered in solution make contact both with DNA and with the corresponding region of the other monomer. These results suggest that these residues become ordered during the process of binding to DNA, forming the dimer interface and thus contributing to the cooperative interaction between monomers.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Schwabe
authors.forename: L
authors.initials: L
authors.lastname: Chapman
authors.forename: J T
authors.initials: JT
authors.lastname: Finch
authors.forename: D
authors.initials: D
authors.lastname: Rhodes
authors.forename: D
authors.initials: D
authors.lastname: Neuhaus
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D021621:Imaging, Three-Dimensional; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011960:Receptors, Estrogen; D004247:DNA