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PDBsum entry 1k6o
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Transcription/DNA
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PDB id
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1k6o
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of a ternary sap-1/srf/c-Fos sre DNA complex.
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Authors
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Y.Mo,
W.Ho,
K.Johnston,
R.Marmorstein.
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Ref.
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J Mol Biol, 2001,
314,
495-506.
[DOI no: ]
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PubMed id
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Abstract
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Combinatorial DNA binding by proteins for promoter-specific gene activation is a
common mode of DNA regulation in eukaryotic organisms, and occurs at the
promoter of the c-fos proto-oncogene. The c-fos promoter contains a serum
response element (SRE) that mediates ternary complex formation with the Ets
proteins SAP-1 or Elk-1 and the MADS-box protein, serum response factor (SRF).
Here, we report the crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA
complex containing the minimal DNA-binding domains of each protein. The
structure of the complex reveals that the SAP-1 monomer and SRF dimer are bound
on opposite faces of the DNA, and that the DNA recognition helix of SAP-1 makes
direct contact with the DNA recognition helix of one of the two SRF subunits.
These interactions facilitate an 82 degrees DNA bend around SRF and a modulation
of protein-DNA contacts by each protein when compared to each of the binary DNA
complexes. A comparison with a recently determined complex containing SRF, an
idealized DNA site, and a SAP-1 fragment containing a SRF-interacting B-box
region, shows a similar overall architecture but also shows important
differences. Specifically, the comparison suggests that the B-box region of the
Ets protein does not significantly influence DNA recognition by either of the
proteins, and that the sequence of the DNA target effects the way in which the
two proteins cooperate for DNA recognition. These studies have implications for
how DNA-bound SRF may modulate the DNA-binding properties of other Ets proteins
such as Elk-1, and for how other Ets proteins may modulate the DNA-binding
properties of other DNA-bound accessory factors to facilitate promoter-specific
transcriptional responses.
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Figure 3.
Figure 3. Details of the DNA interactions by SAP-1 and SRF
within the ternary complex. (a) The interface formed between the
DNA-binding domains of SAP-1, SRF and DNA is shown.
Protein-protein and protein-DNA interactions that are mediated
at this interface are shown. van der Waals interactions are
shown with dotted yellow lines and hydrogen bonds are shown with
broken red lines. (b) A comparison of protein-DNA contacts in
the ternary SAP-1/SRF/c-fos SRE complex and the binary
SAP-1/c-fos SRE complex is shown. The GGA core DNA sequence is
highlighted in green and protein-DNA contacts are indicated with
broken lines for van der Waals interactions and continuous lines
for hydrogen bonds. Protein-DNA contacts that are present in the
ternary complex but not in the binary complex are indicated on
red, and contacts that are in the binary complex but not in the
ternary complex are indicated in blue. Water mediated contacts
in the binary complex are not indicated since water mediated
protein-DNA contacts within the ternary complex are not clearly
resolved for comparison at the resolution of the current
structure. (c) A comparison of protein-DNA contacts in the
ternary SAP-1/SRF/c-fos SRE complex and the binary SRF/a-actinin
DNA complex is shown. The CArG-box DNA sequence is highlighted
in green and protein-DNA contacts are indicated with doted lines
for van der Waals interactions and solid lines for hydrogen
bonds. Color coding is as described in (b) and water-mediated
contacts are omitted.
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Figure 4.
Figure 4. Superposition of the Elk-1 DNA recognition helix
onto the ternary SAP-1/SRF/c-fos SRE DNA complex. The DNA
recognition helix of Elk-1 is shown in aqua with the relative
orientation of the three corresponding side chains (yellow) that
have the most divergent orientation when compared to SAP-1 in
either the binary or ternary complex. This superposition
suggests that the presence of SRF may induce these residues of
Elk-1 to take on a SAP-1 like conformation within a ternary
Elk-1/SRF/c-fos SRE DNA complex and thus facilitate Elk-1
binding to a c-fos SRE DNA sequence.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2001,
314,
495-506)
copyright 2001.
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