Comparative structure analysis of the ETSi domain of ERG3 and its complex with the E74 promoter DNA sequence.

ERG3 (ETS-related gene) is a member of the ETS (erythroblast transformation-specific) family of transcription factors, which contain a highly conserved DNA-binding domain. The ETS family of transcription factors differ in their binding to promoter DNA sequences, and the mechanism of their DNA-sequence discrimination is little known. In the current study, crystals of the ETSi domain (the ETS domain of ERG3 containing a CID motif) in space group P422 and of its complex with the E74 DNA sequence (DNA) in space group C222 were obtained and their structures were determined. Comparative structure analysis of the ETSi domain and its complex with DNA with previously determined structures of the ERGi domain (the ETS domain of ERG containing inhibitory motifs) in space group P622 and of the ERGi-DNA complex in space group P422 were performed. The ETSi domain is observed as a homodimer in solution as well as in the crystallographic asymmetric unit. Superposition of the structure of the ETSi domain on that of the ERGi domain showed a major conformational change at the C-terminal DNA-binding autoinhibitory (CID) motif, while minor changes are observed in the loop regions of the ETSi-domain structure. The ETSi-DNA complex in space group C222 forms a structure that is quite similar to that of the ERG-DNA complex in space group P422. Upon superposition of the complexes, major conformational changes are observed at the 5' and 3' ends of DNA, while the conformation of the core GGA nucleotides was quite conserved. Comparison of the ETSi-DNA structure with known structures of ETS class 1 protein-DNA complexes shows the similarities and differences in the promoter DNA binding and specificity of the class 1 ETS proteins.