Structures of SAP-1 bound to DNA targets from the E74 and c-fos promoters: insights into DNA sequence discrimination by Ets proteins.
SAP-1 is a member of the Ets transcription factors and cooperates with SRF protein to activate transcription of the c-fos protooncogene. The crystal structures of the conserved ETS domain of SAP-1 bound to DNA sequences from the E74 and c-fos promoters reveal that a set of conserved residues contact a GGA core DNA sequence. Discrimination for sequences outside this core is mediated by DNA contacts from conserved and nonconserved protein residues and sequence-dependent DNA structural properties characteristic of A-form DNA structure. Comparison with the related PU.1/DNA and GABPalpha/beta/DNA complexes provides general insights into DNA discrimination between Ets proteins. Modeling studies of a SAP-1/SRF/DNA complex suggest that SRF may modulate SAP-1 binding to DNA by interacting with its ETS domain.
Mo
Y
Y
The Wistar Institute, Department of Chemistry, University of Pennsylvania, Philadelphia 19104, USA.
Vaessen
B
B
Johnston
K
K
Marmorstein
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D016762:Genes, fos; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D050808:ets-Domain Protein Elk-4
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C494193:ELK4 protein, human; C060408:Eip74EF protein, Drosophila; C494194:Elk4 protein, mouse; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D050808:ets-Domain Protein Elk-4; D004247:DNA