Molecular Biology

, Volume 43, Issue 4, pp 612–619 | Cite as

Conserved structural features of ETS domain-DNA complexes

  • A. V. GrishinEmail author
  • A. V. Alexeevsky
  • S. A. Spirin
  • A. S. Karyagina
Structural-Functional Analysis of Biopolymers and Their Complexes


ETS proteins are a family of widespread transcription factors that regulate the expression of many animal genes. Structurally, ETS proteins are characterized by a conserved DNA-binding ETS domain, which recognizes DNA sequences containing the trinucleotide GGA. The structural features of ETS domain-DNA complexes were analyzed, and conserved contacts important in terms of interaction stability and specificity were identified. The analysis revealed nine conserved hydrogen bonds with oxygens of DNA backbone phosphates, two bidentate hydrogen bonds with DNA major groove atoms, one conserved hydrophobic cluster located on the protein-DNA interface and important for binding site recognition, and 12 conserved water molecules presumably mediating the ETS domain-DNA interaction. The results are represented in specialized data bank of protein-DNA complexes (NPIDB).

Key words

ETS family protein-DNA interaction comparative analysis of related structures eukaryotic transcription factor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Donaldson L.W., Petersen J.M., Graves B.J., McIntosh L.P. 1994. Secondary structure of the ETS domain places murine Ets-1 in the superfamily of winged helix-turn-helix DNA-binding proteins. Biochemistry. 33, 13509–13516.PubMedCrossRefGoogle Scholar
  2. 2.
    Nunn M.F., Seeburg P.H., Moscovici C., Duesberg P.H. 1983. Tripartite structure of the avian erythroblastosis virus E26 transforming gene. Nature ( Lond.). 306, 391–395.CrossRefGoogle Scholar
  3. 3.
    Wasylyk B., Hahn S.L., Giovane A. 1993. The Ets family of transcription factors. Eur. J. Biochemistry. 211(1–2), 7–18.CrossRefGoogle Scholar
  4. 4.
    Oikawa T., Yamada T. 2003. Molecular biology of the Ets family of transcription factors. Gene. 303, 11–34.PubMedCrossRefGoogle Scholar
  5. 5.
    Bassuk A.G., Leiden J.M. 1995. A direct physical association between ETS and AP-1 transcription factors in normal human T cells. Immunity. 3, 223–237.PubMedCrossRefGoogle Scholar
  6. 6.
    Bassuk A.G., Anandappa R.T., Leiden J.M. 1997 Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells. J. Virol. 71, 3563–3573.PubMedGoogle Scholar
  7. 7.
    Li R., Pei H., Watson D.K., Papas T.S. 2000. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene. 19, 745–753.PubMedCrossRefGoogle Scholar
  8. 8.
    Pei H., Yordy J.S., Leng Q., Zhao Q., Watson D.K., Li R. 2003. EAPII interacts with ETS1 and modulates its transcriptional function. Oncogene. 22, 2699–2709.PubMedCrossRefGoogle Scholar
  9. 9.
    Yordy J.S., Li R., Sementchenko V.I., Pei H., Muise-Helmericks R.C., Watson D.K. 2004. SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion. Oncogene. 23, 6654–6665.PubMedCrossRefGoogle Scholar
  10. 10.
    Wasylyk B., Hagman J., Gutierrez-Hartmann A. 1998. Ets transcription factors: Nuclear effectors of the Ras-MAP kinase signaling pathway. Trends Biochem. Sci. 23, 213–216.PubMedCrossRefGoogle Scholar
  11. 11.
    Spirin S., Titov M., Karyagina A., Alexeevski A. 2007. NPIDB: A database of nucleic acids-protein interactions. Bioinformatics. 23, 3247–3248.PubMedCrossRefGoogle Scholar
  12. 12.
    Krissinel E., Henrick K. 2004. Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Cryst. 60, 2256–2268.Google Scholar
  13. 13.
    Nicholas K.B., Nicholas H.B. Jr., Deerfield D.W. 1997. GeneDoc: Analysis and visualization of genetic variation. EMBNEW News. 4, 1–4.Google Scholar
  14. 14.
    Sayle R.A., Milner-White E.J. 1995. RASMOL: Biomolecular graphics for all. Trends Biochem. Sci. 20, 374–376.PubMedCrossRefGoogle Scholar
  15. 15.
    DeLano W.L. 2003. The PyMOL Molecular Graphics System. San Carlos, CA: DeLano Scientific.Google Scholar
  16. 16.
    Alexeevski A., Spirin S., Alexeevski D., Klychnikov O., Ershova A., Titov M., Karyagina A. 2004. CluD, a program for the determination of hydrophobic clusters in 3D structures of protein and protein-nucleic acids complexes. Biofizika (Moscow). 48,Suppl. 1, 146–156.Google Scholar
  17. 17.
    Aksianov E., Zanegina O., Alexeevski A., Karyagina A., Spirin S. 2008. Conserved water molecules in X-ray structures highlight the role of water in intramolecular and intermolecular interactions. J. Bioinform. Comp. Biol. 6, 775–788.CrossRefGoogle Scholar
  18. 18.
    Tang Y., Nilsson L. 1998. Interaction of human SRY protein with DNA: A molecular dynamics study. Proteins. 31, 417–433.PubMedCrossRefGoogle Scholar
  19. 19.
    Gorfe A.A., Jelesarov I. 2003. Energetics of sequence-specific protein-DNA association: Computational analysis of integrase Tn916 binding to its target DNA. Biochemistry. 42, 11568–11576.PubMedCrossRefGoogle Scholar
  20. 20.
    Lett C.M., Berghuis A.M., Frey H.E., Lepock J.R., Guillemette J.G. 1996. The role of a conserved water molecule in the redox-dependent thermal stability of iso-1-cytochrome c. J. Biol. Chem. 271, 29088–29093.PubMedCrossRefGoogle Scholar
  21. 21.
    Fauman E.B., Rutenber E.E., Maley G.F., Maley F., Stroud R.M. 1994. Water-mediated substrate/product discrimination: The product complex of thymidylate synthase at 1.83 Å. Biochemistry. 33, 1502–1511.PubMedCrossRefGoogle Scholar
  22. 22.
    Likic V.A., Juranic N., Macura S., Prendergast F.G. 2000. A “structural” water molecule in the family of fatty acid binding proteins. Protein Sci. 9, 497–504.PubMedGoogle Scholar
  23. 23.
    Mustata G., Briggs J.M. 2004. Cluster analysis of water molecules in alanine racemase and their putative structural role. Protein Eng. Des. Sel. 17, 2232–2234.CrossRefGoogle Scholar
  24. 24.
    Karyagina A., Ershova A., Spirin S., Alexeevski A. 2005. The role of water in homeodomain-DNA interaction. In: Bioinformatics of Genome Regulation and Structure. Eds Kolchanov N., Hofestaedt R. N.Y.: Springer Science + Business Media, Inc., pp. 247–257.Google Scholar
  25. 25.
    Joachimiak A., Haran T.E., Sigler P.B. 1994. Mutagenesis supports water mediated recognition in the Trp repressor-operator system. EMBO J. 13, 367–372.PubMedGoogle Scholar
  26. 26.
    Ogata K., Wodak S.J. 2002. Conserved water molecules in MHC class-I molecules and their putative structural and functional roles. Protein Eng. 15, 697–705.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  • A. V. Grishin
    • 1
    Email author
  • A. V. Alexeevsky
    • 2
    • 3
  • S. A. Spirin
    • 2
    • 3
  • A. S. Karyagina
    • 1
    • 4
  1. 1.All-Russia Institute of Agricultural BiotechnologyRussian Academy of Agricultural SciencesMoscowRussia
  2. 2.Belozersky Institute of Physico-Chemical BiologyMoscow State UniversityMoscowRussia
  3. 3.Institute of System StudiesRussian Academy of SciencesMoscowRussia
  4. 4.Gamaleya Institute of Epidemiology and MicrobiologyRussian Academy of Medical SciencesMoscowRussia

Personalised recommendations