Chain A: The ERa-complex is Cartoons, colored Structure. Helices are numbered at their N-termini. Helix 12 is magenta ("H12A"); RAL is Spacefill, colored CPK.
Chain B: The ERb-complex is Backbone, colored green. Helix 12 is labelled "H12B" at its C-terminus. (RAL in the original structure is not shown.)
(The residue numbering here is 300 less than standard ERa numbering and 302 less than standard ERb numbering.)
See Brzozowski (1997) & Pike (1999).
The numbered "Highlight" buttons above display details of the raloxifene-binding region on the ER LBD. The following paragraphs briefly describe the displays.
1 a. ERa-RAL complex. The principal interacting residues are shown. (Slab on) Polar side chains are Ball & Stick, colored CPK; apolar residues are Sticks.
The comparable interacting residues on ERb can be added to the display as green, Sticks.
H-bond distances in the ERa structure are in Å.
1 b. Chains A and B All interacting residues are shown with colored
contact atoms. ER atoms <4.5 Å from RAL 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.
These two residues are the only sequence differences in direct contact
with RAL.
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.
[1err.pdb]
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.
[1qkn.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.
