PDBsum entry 1k6o

Transcription/DNA

PDB id: 1k6o

Contents

Protein chains

89 a.a. *

85 a.a. *

DNA/RNA

* Residue conservation analysis

PDB id:

1k6o

Name:

Transcription/DNA

Title:

Crystal structure of a ternary sap-1/srf/c-fos sre DNA complex

Structure:

5'-d( Cp Ap Cp Ap Gp Gp Ap Tp Gp Tp Cp Cp Ap Tp Ap Tp Tp Ap Gp Gp Ap Cp A)-3'. Chain: d. Engineered: yes. Other_details: c-fos sre sequence strand 1. 5'-d( Tp Gp Tp Cp Cp Tp Ap Ap Tp Ap Tp Gp Gp Ap Cp Ap Tp Cp Cp Tp Gp Tp G)-3'. Chain: e. Engineered: yes.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: sap. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: srf.

Biol. unit:

Pentamer (from PQS)

Resolution:

3.19Å R-factor: 0.220 R-free: 0.276

Authors:

Y.Mo,W.Ho,K.Johnston,R.Marmorstein

Key ref:

Y.Mo et al. (2001). Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex. J Mol Biol, 314, 495-506. PubMed id: 11846562 DOI: 10.1006/jmbi.2001.5138

Date:

16-Oct-01 Release date: 17-Jan-02

Protein chain

P28324  (ELK4_HUMAN) -  ETS domain-containing protein Elk-4 from Homo sapiens

Seq: 431 a.a.

Struc: 89 a.a.

Protein chains

P11831  (SRF_HUMAN) -  Serum response factor from Homo sapiens

Seq: 508 a.a.

Struc: 85 a.a.

DNA/RNA chains

C-A-C-A-G-G-A-T-G-T-C-C-A-T-A-T-T-A-G-G-A-C-A 23 bases

T-G-T-C-C-T-A-A-T-A-T-G-G-A-C-A-T-C-C-T-G-T-G 23 bases

Enzyme reactions

• Enzyme class: Chains A, B, C: E.C.?

DOI no: 10.1006/jmbi.2001.5138

J Mol Biol 314:495-506 (2001)

PubMed id: 11846562

Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex.

Y.Mo, W.Ho, K.Johnston, R.Marmorstein.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 314, 495-506) copyright 2001.

Figures were selected by an automated process.