Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex.
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.
Mo
Y
Y
The Wistar Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Ho
W
W
Johnston
K
K
Marmorstein
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D019281:Dimerization; D005800:Genes, Fungal / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D026341:Minichromosome Maintenance 1 Protein / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry* / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D016415:Sequence Alignment; D026362:Serum Response Factor / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494193:ELK4 protein, human; C000715470:MAS1 protein, human; D046911:Macromolecular Substances; D026341:Minichromosome Maintenance 1 Protein; D021122:Protein Subunits; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; D004247:DNA