Left model: the subunit is Cartoons, colored Structure; RAL is Ball & Stick, colored CPK. The 12 helices are numbered at their N-termini.
Right model: the subunit is Cartoons, colored green, except for helix 12 (magenta). RAL is Spacefill, colored blue. The N- and C-termini are labeled. See Brzozowski, et al. (1997) Fig. 1b.
The numbered "Highlight" buttons above display details of the RAL and the Helix 12 sites on ER. The following paragraphs briefly describe the displays.
1. Close-up of the RAL binding site. H-bonding residues are Ball & Stick; apolar residues are shown as Sticks, colored CPK. In addition to the H-bonds found in the EST complex (E353, R394, and H524), Asp 351 H-bonds to the piperizine nitrogen in the "pendant extension" of RAL. See Brzozowski, Fig. 2b.
H-bond distances in Å. See Brzozowski, Fig. 2a.
Close contacts: ER atoms <4.5 Å from RAL are yellow. Display the contact atoms as Spacefill or as Sticks (+Dot surface).
2. Close-up of the Helix 12 binding site. Helix 12 residues are
shown as Sticks, colored green. The Ca carbons
of Asp 538, Glu 542, and Asp 545 on the surface of H12 are colored brown.
See Brzozowski, Fig. 3b.
Close contacts: ER atoms <4.5 Å from Helix 12 are yellow;
Helix 12 atoms <4.5 Å from the ER are blue.
Display the ER binding site as Spacefill and/or the helix 12
contacts as a Dot surface.
3. Sequence Comparison between ERa
and ERb. The aligned sequences (Clustal W) are
shown by category on the left model: Identical (blue, 59%); Comparable
(cyan, 25%); Similar (Spacefill, orange, 5%); and Different (Spacefill,
red, 11%).
Most of the differences between the isoforms are on the surface, e.g.
helix 10 at the top. Helix 12 and its binding site is nearly identical;
the dimer interface is highly conserved. 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
This estrogen receptor structure is 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; 2.6 Å; R = 0.22]
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.
