Estrogen Receptor: Helix 12 Slide Show
A. ERa: All six structures
ERa-EST superimposed with:
B. ERa-RAL
C. ERa-OHT
D. ERb-GEN
E. ERa-EST (mutant)
F. ERa-EST(tetramer)
Helix 12 of the Estrogen Receptor assumes several positions in various ligand complexes
Five ER-ligand complexes were aligned with ERa-EST to produce the superimposed models shown. ERa-EST (green) is shown in each JPEG image. The other complexes are shown as gray Backbone; color-coding of the complexes is indicated on each "slide" (choose from the links at right above). The colored segments correspond to comparable regions preceding and including Helix 12; Helix 12 itself is shown as thicker Backbone.
The abbreviations used are: EST (17b-estradiol); RAL (raloxifene); OHT (4-hydroxytamoxifen); GEN (genistein). The "mutant" is a triple Cys->Ser substitution; "tetramer" refers to an unusal tetrameric crystal form of ER. (EST is shown in each image; RAL, OHT, and GEN are not shown.)

References   [PDB coordinate files]
A. & B. ERa-EST & ERa-RAL: Brzozowski, A. M., Pike, A. C., Dauter, Z., Hubbard, R. E., Bonn, T., Engstrom, O., Ohman, L., Greene, G. L., Gustafsson, J. A., Carlquist, M. (1997) "Molecular basis of agonism and antagonism in the oestrogen receptor". Nature 389:753.     PubMed.     [1ere.pdb; 1err.pdb]
C. ERa-OHT: Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L., Kushner, P. J., Agard, D. A., Greene, G. L. (1998) "The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen". Cell 95 :927.     PubMed.     [3ert.pdb]
D. ERb-GEN: Pike, A. C. W., Brzozowski, A. M., Hubbard, R. E., Bonn, T., Thorsell, A.-G., Engstrom, O., Ljunggren, J., Gustaffson, J.-A., Carlquist, M. (1999) "Structure of the Ligand-Binding Domain of Oestrogen Receptor Beta in the Presence of a Partial Agonist and a Full Antagonist." Embo J. 18:101.     PubMed.     [1qkm.pdb]
E. ERa-EST (mutant): Gangloff M, Ruff M, Eiler S, Duclaud S, Wurtz JM, Moras D. (2001) "Crystal structure of a mutant hERalpha ligand-binding domain reveals key structural features for the mechanism of partial agonism". J Biol Chem 276:15059.     PubMed.     [1qkt.pdb]
F. ERa-EST (tetramer): Tanenbaum, D. M., Wang, Y., Williams, S. P., Sigler, P. B. (1998) "Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains". Proc Natl Acad Sci U S A 95:5998.     PubMed.     [1a52.pdb]

"Helix 12 Gallery": Interactive Chime displays of ERa-EST superimposed with the five ER-antagonist (SERM) JPEGs shown here.

ERback Return to ER Intro Page

6.16.01