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Review
. 2000;2(5):353-9.
doi: 10.1186/bcr80. Epub 2000 Jul 7.

Estrogen receptor transcription and transactivation: Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors

M Ruff  1 , M Gangloff, J M Wurtz, D Moras
Affiliations
Review

Estrogen receptor transcription and transactivation: Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors

M Ruff et al. Breast Cancer Res. 2000.

Abstract

Estrogen receptors are members of the nuclear receptor steroid family that exhibit specific structural features, ligand-binding domain sequence identity and dimeric interactions, that single them out. The crystal structures of their DNA-binding domains give some insight into how nuclear receptors discriminate between DNA response elements. The various ligand-binding domain crystal structures of the two known estrogen receptor isotypes (alpha and beta) allow one to interpret ligand specificity and reveal the interactions responsible for stabilizing the activation helix H12 in the agonist and antagonist positions.

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Figures

Figure 1
Figure 1
Schematic representation of the functional domain organization of nuclear receptors. The percentages of identity with human ERα are given for the DBD and LBD of human ERβ, human PR, and human RXRα. (b) The consensus sequence for steroid nuclear receptors and the ER response element.
Figure 2
Figure 2
Schematic representation of the domain C of nuclear receptors, formed by a zinc finger motif. The residues making the 'P box' and the 'D box' are shown. (b) The three-dimensional X-ray structure of a dimer of ER DBD interacting with DNA. Helices 10 and 11 and some residues of helices 8 and 9 are involved in the interface.
Figure 3
Figure 3
Three-dimensional structure of the wild-type ER LBD monomer, with the β-sheet colored in blue. (b) Anchoring of the estradiol in the active site. The 3-hydroxyl group is hydrogen-bonded to Arg 394 and Glu 353 and a structural water molecule represented in green. The 17-β hydroxyl group forms a hydrogen bond with His 524. (c) Superposition of the three-dimensional structure of ERα LBD complexed with estradiol (green conformation), raloxifen and tamoxifen (red and blue conformations). (d) The ligand pocket of human ERβ showing the residues that are different in human ERα. The ERβ residue names and numbers are shown in black, the ERα residue names are in grey.
Figure 4
Figure 4
Sequence alignment of coactivator NR boxes and H12 from ERα and ERβ. (b) Superposition of the H12 structure from ERα complexed with tamoxifen and the ERα structure complexed with DES and a NR box peptide from TIF2/GRIP1.
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