Chain A: The DES-complex is Cartoons, colored cyan. Helices 3, 4, and 5 are light blue; helix 12 is magenta ("H12A"); DES is Spacefill, colored green. The NR Box II peptide is Cartoons, colored gold.
Chain B: The OHT-complex is Backbone, colored blue, except for helix 12 ("H12B", magenta). OHT is not shown.
(The residue numbering here is 293 less than standard ER numbering.)
See Shiau, et al. (1998) Fig. 2A & B (right).
Each ER complex is highlighted separately (in a plausible sequence of interconversion steps):
- 1. ER-OHT complex (two steps).
- a. Activator (the peptide, in this model) and DES (or EST) dissociate;
- b. H12 occupies the AF II pocket. (The "absent hormone" is represented by its Dot surface.)
- 2. ER-DES complex (four steps).
- a. Mobile H12 moves (out of the way);
- b. DES (or EST) binds;
- c. H12 closes the lid;
- d. Activator (peptide, here) binds to the AF II site.
The major difference between the two complexes is the position of helix 12. In the DES complex, helix 12 forms a "trap door" on the hormone binding pocket. This allows the NR peptide to occupy its site on the ER. In the OHT complex (and maybe in the apo-receptor), helix 12 moves into the NR peptide site, thereby preventing transcriptional activation.
Page Top
The estrogen receptor structures are described in 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.
[3erd.pdb & 3ert.pdb]
Structure alignments were done at the Combinatorial Extension Server.
Additional ER structures:
A. Estrogen Receptora
ERa complexes with bound:
Estradiol (EST),
an agonist.
Raloxifene (RAL),
an antagonist.
Diethylstilbestrol (DES),
an agonist & the NR Box II peptide.
Tamoxifen (OHT),
an antagonist.
(Estradiol (EST),
in an unusual tetrameric structure.)
B. Estrogen Receptorb
ERb complexes with bound:
Genistein (GEN),
a partial agonist.
Raloxifene (RAL),
an antagonist.
C. Structural Alignments Pairwise superimposed comparisons:
ERa
(EST) and ERb (GEN),
ERa vs. ERb
in agonist complexes.
ERa
(RAL) and ERb (RAL),
ERa vs. ERb
in antagonist complexes.
ERa:
DES and OHT, ERa: agonist
vs. antagonist complex.
ERa:
EST, Wild type ER vs. a triple mutant (Helix 12 in the antagonist
conformation).
ERa:
EST, The Brzozowski, et al. (1997) vs. Tanenbaum, et al. (1998)
models.
"Helix 12 Gallery":
ERa-EST vs. All five ER-antagonist
(SERM) models.
D. DNA-Binding Domain:
ER-DBD Complex
Base pair & backbone contacts.
