This tetrameric form is most likely a crystallographic artefact. The solution structure is known to be dimeric. The tetramer is stabilized by two interchain disulfide bonds (labelled "S-S" above) and by the helix 12 contacts between adjacent dimers. Nevertheless, the model shows the "high degree of positional variability exhibited by . . . the aberrant position of helix 12".
Monomer subunits A and D are Cartoons, colored Structure; EST is Spacefill, colored green. The 12 helices are numbered in chain A.
Monomer subunits B and C are Cartoons, colored blue. The N- and C-termini of chain B are labeled. See Tanenbaum, et al. (1998) Fig. 2A.
The numbered "Highlight" buttons above display details of the estradiol and Helix 12 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 EST plane are shown as Sticks, colored CPK. (Slab Mode on) H-bond distances in Å. See Tanenbaum, Fig. 3A & C.
a. Close contacts: ER atoms <4.5 Å from EST are yellow. Display the contact atoms as Spacefill or as Sticks (dots).
b. Conserved residues in all steroid receptors (green-blinker). See Tanenbaum, Fig. 3C.
When this model was aligned with the dimer model of Brzozowski, et al. (1997), the superimposed structures were nearly identical in the EST-binding site region. (See the link below under "Structural Alignments".)
2. Close-up of the Helix 12 binding site on chain C. Helix 12
residues of chain A are shown as Sticks, colored magenta. It is bound to
part of the H12 binding pocket of chain C. See Tanenbaum Fig. 1B.
Helix 12 or its site can be highlighted as follows:
Close contacts: Chain C atoms <4.5 Å from Helix 12
are yellow; Helix 12 atoms of chain A <4.5 Å from chain C are
green.
View the chain C binding site as Spacefill and/or the Helix
12 with a Dot surface.
3. Comparison with the dimer structure of Brzozowski, et al. (1997).
The H12 interface side chains are Sticks. Those found only in this structure
are red; those found only in the Brzozowski structure are green; those
found in both are yellow.
Additional highlight buttons:
Brzozowski H12 contact residues: Spacefill, green.
Tanenbaum H12 contact residues: Spacefill, red.
H12 contact residues in both models: Spacefill, yellow.
The helix 12 binding pocket here is only about half the size of that
seen in other ER-agonist structures.
Page Top
This estrogen receptor structure is described in Tanenbaum,
D. M., Wang, Y., Williams, S. P., Sigler, P. B. (1998) "Crystallographic
comparison of the estrogen and progesterone receptor's ligand binding domains".
Proc Natl Acad Sci U S A 95:5998.
PubMed.
[1a52.pdb; 2.8 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.
