Chain A: The ERa-complex is Cartoons, colored Structure. Helices are numbered at their N-termini. Helix 12 is magenta ("H12A"); EST is Spacefill, colored CPK.
Chain B: The ERb-complex is Backbone, colored green. Helix 12 is labelled "H12B" at its C-terminus. (GEN in the original structure is not shown.)
(The residue numbering here is 300 less than standard ERa numbering.)
See Brzozowski (1997) & Pike (1999).
The numbered "Highlight" buttons above display details of the estradiol-binding region on the ER LBD. The following paragraphs briefly describe the displays.
1 a. ERa-EST complex. The principal interacting residues are shown. (Slab on)
H-bond distances are in Å.
1 b. Chains A and B All interacting residues are shown with colored contact atoms. ER atoms <4.5 Å from EST are colored yellow in ERa and green in ERb. See Brzozowski (1997) Fig. 2a.
The following can be displayed separately:
ERa, only.
ERb, only.
EST-interacting residues, only. Interacting residues are shown as Sticks, colored CPK. See Brzozowski (1997) Fig. 2c.
Note: the buttons in this group leave the "contact atoms" selected. Thus, any choice of display or color from the Chime menu can be used for additional highlighting.
The largest difference in the overall structure of the two complexes is the movement of the mainchain and side chains from lower right (in ERa) to upper left in ERb (e.g. toggle between the "ERa, only" and the "ERb, only" buttons). In addition, note that L84 (Leu 384) in ERa is replaced by the larger M82 (Met 384) in ERb and that M121 (Met 421) in ERa is replaced by the smaller I119 in ERb. These two residues are the only sequence differences in direct contact with EST.
2. Sequence Comparison The aligned sequences (Clustal W) are
shown by category on ERa: Identical (blue);
Comparable (cyan); Similar (Spacefill, orange); and Different (Spacefill,
red). ERb is shown as Backbone, colored white.
Most of the differences between the isoforms are on the surface, e.g.
helix 10 at the top. Helix 12 and its two alternative binding sites are
nearly identical. In addition, there are other patches of highly conserved
surface residues.
Note: the small buttons in this group select one of the four categories.
Thus, any choice of display or color from the Chime menu can be used for
additional highlighting.
Page Top
The estrogen receptor structures are described in 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; 3.1 Å; R = 0.22]
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 1.8 Å; R = 0.22]
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.
