title: Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor.
abstract: We have identified a region within the steroid binding domain of the mouse estrogen receptor that is required for both receptor dimerization and high affinity DNA binding. Analysis of sequences in this region revealed that a heptad repeat of hydrophobic residues was conserved in all members of the nuclear receptor superfamily. Single amino acid substitutions of residues in the N-terminal half, but not the C-terminal half, of the repeat prevented receptor dimerization. Steroid binding was abolished by point mutations in the center of the conserved region, implying that the steroid binding and dimerization domains overlap. The role of this region in steroid receptor function is discussed in relation to other models of protein dimerization and DNA binding.
authors.affiliation: Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, England.
authors.forename: S E
authors.initials: SE
authors.lastname: Fawell
authors.forename: J A
authors.initials: JA
authors.lastname: Lees
authors.forename: R
authors.initials: R
authors.lastname: White
authors.forename: M G
authors.initials: MG
authors.lastname: Parker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D001665:Binding Sites; D002872:Chromosome Deletion; D008024:Ligands; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D009842:Oligopeptides; D014176:Protein Biosynthesis; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D000906:Antibodies; D008024:Ligands; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D009842:Oligopeptides; D011960:Receptors, Estrogen