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

Ruby Sharma, Shanti Gangwar, Ajay K. Saxena

Research output: Contribution to journalArticle

Abstract

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 P41212 and of its complex with the E74 DNA sequence (DNA9) in space group C2221 were obtained and their structures were determined. Comparative structure analysis of the ETSi domain and its complex with DNA9 with previously determined structures of the ERGi domain (the ETS domain of ERG containing inhibitory motifs) in space group P65212 and of the ERGi-DNA12 complex in space group P41212 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-DNA9 complex in space group C2221 forms a structure that is quite similar to that of the ERG-DNA12 complex in space group P41212. Upon superposition of the complexes, major conformational changes are observed at the 5′ and 3′ ends of DNA9, while the conformation of the core GGA nucleotides was quite conserved. Comparison of the ETSi-DNA9 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.X-ray structures of the ETSi domain of human ERG3 and of its complex with the E74 promoter DNA sequence are reported. Comparison of the ETSi-DNA9 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.

Original languageEnglish (US)
Pages (from-to)656-663
Number of pages8
JournalActa Crystallographica Section F: Structural Biology Communications
Volume74
Issue number10
DOIs
StatePublished - Oct 1 2018
Externally publishedYes

Fingerprint

Erythroblasts
DNA sequences
deoxyribonucleic acid
DNA
Proteins
Transcription Factors
charge injection devices
proteins
Conformations
Nucleotides
Genes
X rays
Crystals
nucleotides
genes
X-Rays
discrimination

Keywords

  • comparative structure analysis
  • E74 promoter DNA
  • ERG3
  • ETS transcription factor
  • prostate cancer
  • X-ray structure

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Condensed Matter Physics

Cite this

Comparative structure analysis of the ETSi domain of ERG3 and its complex with the E74 promoter DNA sequence. / Sharma, Ruby; Gangwar, Shanti; Saxena, Ajay K.

In: Acta Crystallographica Section F: Structural Biology Communications, Vol. 74, No. 10, 01.10.2018, p. 656-663.

Research output: Contribution to journalArticle

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