Left model: the subunit is Cartoons, colored Structure; EST is Ball & Stick, colored CPK. The 12 helices are numbered.
Right model: the subunit is Cartoons, colored green, except for helix 12 (magenta). EST is Spacefill, colored blue. The N- and C-termini are labeled. See Brzozowski, et al. (1997) Fig. 1b.
The overall architecture of ER (and the NR superfamily) is described as an "a-sandwich" where helices 5, 6, 9, and 10 form a middle layer; the antiparallel helices 7, 8, and 11, on one side, and helices 2-4 on the other side surround the central core.
The numbered "Highlight" buttons above display details of the estradiol, Helix 12, and dimer interface sites on ER. The following paragraphs briefly describe the displays.
1. Close-up of the EST binding site. H-bonding residues are Ball & Stick. Apolar residues in the plane of the ligand are shown as Sticks, colored CPK. Glu 353 and Arg 394 are hydrogen bonded to the hydoxyl at one end of EST; the other end is anchored by a H-bond to His 524. These three interactions are found in all of the ER-ligand complexes. The rest of the binding site is a large cavity lined with hydrophobic side chains.
H-bond distances in Å. See Brzozowski, Fig. 2a.
Close contacts: ER atoms <4.5 Å from estradiol are yellow. This rather generous contact distance was used so as to display most of the side chains that surround EST. A more realistic set of van der Waals interactions is probably seen at 4.0 Å using the "Closer contacts" button. Display either set of "contact atoms" as Spacefill or as Sticks (Dot surface).
Deselect Slab Mode (under Options) if the highlighted region moves out of view.
2. Close-up of the Helix 12 binding site. Helix 12 residues are
shown as Sticks, colored blue. The Ca carbons
of Asp 538, Glu 542, and Asp 545 on the surface of H12 are colored brown.
See Brzozowski, Fig. 3a.
Close contacts: ER atoms <4.5 Å from Helix 12 are yellow;
Helix 12 atoms <4.5 Å from the ER are green.
Display the ER binding site as Spacefill and/or the helix 12
contacts as a Dot surface.
3. The dimer interface contacts. The interface residues are Sticks;
the close contacts (atoms <4.5 Å) are yellow on chain A and green
on chain B.
Display the chain A contacts as Spacefill.
Display the chain B contacts as a Dot surface.
Display the chain A polar residues as Spacefill & red; chain
A apolar residues as Spacefill & blue.
Label the chain B interface residues.
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.
[1ere.pdb; 3.1 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.
