 |
PDBsum entry 1by4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gene regulation/DNA
|
PDB id
|
|
|
|
1by4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural basis of rxr-Dna interactions.
|
|
|
Authors
|
|
Q.Zhao,
S.A.Chasse,
S.Devarakonda,
M.L.Sierk,
B.Ahvazi,
F.Rastinejad.
|
|
|
Ref.
|
|
J Mol Biol, 2000,
296,
509-520.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The 9-cis retinoic acid receptor, RXR, binds DNA effectively as a homodimer or
as a heterodimer with other nuclear receptors. The DNA-binding sites for these
RXR complexes are direct repeats of a consensus sequence separated by one to
five base-pairs of intervening space. Here, we report the 2.1 A crystal
structure of the RXR-DNA-binding domain as a homodimer in complex with its
idealized direct repeat DNA target. The structure shows how a gene-regulatory
site can induce conformational changes in a transcription factor that promote
homo-cooperative assembly. Specifically, an alpha-helix in the T-box is
disrupted to allow efficient DNA-binding and subunit dimerization. RXR displays
a relaxed mode of sequence recognition, interacting with only three base-pairs
in each hexameric half-site. The structure illustrates how site selection is
achieved in this large eukaryotic transcription factor family through discrete
protein-protein interactions and the use of tandem DNA binding sites with
characteristic spacings.
|
|
|
|
|
|
|
|
Figure 3.
Figure 3. Protein-DNA and protein-protein interactions at
the dimer interfaces. (a) Close-up view of the protein-protein
contacts in the DR1 complex formed by subunits 1 and 2, and
equivalently by subunits 3 and 4. The pink bars indicate the
position of the spacer base-pair(s). Side-chains shown are only
those making DNA or dimerization contacts. Hydrogen bonding
between the side-chains of residues 49, 52 and 74, which form
the dimerization contacts, are shown by broken lines. Figures
were generated with Ribbons [Carson and Bugg 1986]. (b) The
corresponding view at the "DR2" site. (c) Surface
complementarity in the protein-protein interface on DR1, with
subunit 1 shown in red and subunit 2 shown in white. The
location of the DNA is shown for reference, with the 5' end
pointing up [Nicholls et al 1991]. (d) The corresponding view at
the "DR2" interface, with subunit 2 (white) and subunit 3
(blue). (e) Fluorescence anisotropy measurements showing the
binding of RXR-DBD to DR1 (black circles) and DR2 (red squares).
The maximal values for fluorescence aniostropy differ for the
DR1 and DR2 plots, as expected from the different binding
geometries and solution reorientation properties of these
complexes.
|
|
Figure 6.
Figure 6. Similarities among the structurally characterized
DBD-DNA complexes. Comparison of the (a) RXR DBD-DNA complex on
DR1 with those of the (b) RXR-TR DBD on DR4 [Rastinejad et al
1995], (c) the RevErb homodimer on DR2 [Zhao et al 1998] and (d)
the glucocorticoid DBD complex on a symmetric repeat Pal3 [Luisi
et al 1991]. In each case, the DNA is shown with the 5' end at
the top, and the spacer base-pairs are colored pink.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2000,
296,
509-520)
copyright 2000.
|
|
|
|
|
|
|
