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A new pattern for helix–turn–helix recognition revealed by the PU.l ETS–domain–DNA complex

Nature volume 380, pages 456–460 (1996)Cite this article

Abstract

THE Ets family of transcription factors, of which there are now about 35 members1,2, regulate gene expression during growth and development. They share a conserved domain of around 85 amino acids3 which binds as a monomer to the DNA sequence 5'-C/ AGGAA/T-3'. We have determined theocrystal structure of an ETS domain complexed with DNA, at 2.3-Å resolution. The domain is similar to α+β (winged) 'helix–turn–helix' proteins and interacts with a ten-base-pair region of duplex DNA which takes up a uniform curve of 8°. The domain contacts the DNA by a novel loop–helix–loop architecture. Four of the amino acids that directly interact with the DNA are highly conserved: two arginines from the recognition helix lying in the major groove, one lysine from the 'wing' that binds upstream of the core GGAA sequence, and another lysine, from the 'turn' of the 'helix–turn–helix' motif, which binds downstream and on the opposite strand.

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References

  1. Wasylyk, B., Hahn, S. L. & Glovane, A. Eur. J. Biochem. 211, 7–18 (1993).

    Article  CAS  Google Scholar 

  2. Moreau-Gachelin, F. Biochim. biophys. Acta 1198, 149–163 (1994).

    PubMed  Google Scholar 

  3. Karim, F. et al. Genes Dev. 4, 1451–1453 (1990).

    Article  CAS  Google Scholar 

  4. Klemsz, M. J., McKercher, S. R., Celada, A., Van Beveren, C. & Maki, R. A. Cell 61, 113–124 (1990).

    Article  CAS  Google Scholar 

  5. Moreau-Gachelin, F., Mattei, M. G., Tambourin, R. & Tavitian, A. Oncogene 4, 1449–1456 (1989).

    CAS  PubMed  Google Scholar 

  6. Pio, F. et al. J. biol. Chem. 270, 24258–24263 (1995).

    Article  CAS  Google Scholar 

  7. Liang, H. et al. Nature struct. Biol. 1, 871–875 (1994).

    Article  CAS  Google Scholar 

  8. Donaldson, L. W., Petersen, J. M., Graves, B. J. & Mclntosh, L P. EMBO J. 15, 125–134 (1996).

    Article  CAS  Google Scholar 

  9. Werner, M. H. et al. Cell 83, 761–771 (1995).

    Article  CAS  Google Scholar 

  10. Schultz, S. C., Shields, G. C. & Steitz, T. A. Science 253, 1001–1007 (1991).

    Article  ADS  CAS  Google Scholar 

  11. Ramakrishnan, V., Finch, J. T., Graziano, V., Lee, P. L. & Sweet, R. M. Nature 362, 219–223 (1993).

    Article  ADS  CAS  Google Scholar 

  12. Clark, K. L., Halay, E. D., Lai, E. & Burley, S. K. Nature 364, 412–420 (1993).

    Article  ADS  CAS  Google Scholar 

  13. Harrison, C. J., Bohm, A. A. & Nelson, H. C. M. Science 263, 224–227 (1994).

    Article  ADS  CAS  Google Scholar 

  14. Mavrothalassitis, G., Fisher, R. J., Smyth, F., Watson, D. K. & Papas, T. S. Oncogens 9, 425–435 (1994).

    CAS  Google Scholar 

  15. Werner, M. H., Clore, G. M., Gronenborn, A. M., Kondoh, A. & Fisher, R. J. FEBS Lett. 345, 125–130 (1994).

    Article  CAS  Google Scholar 

  16. Brünger, A. T. Nature 355, 472–475 (1992).

    Article  ADS  Google Scholar 

  17. Furey, W. & Swaminathan, S. Am. crystallogr. Ass. Meeting 18, 73 (1990).

    Google Scholar 

  18. Wang, B. C. Methods Enzymol. 115, 90–112 (1985).

    Article  CAS  Google Scholar 

  19. Jones, T. A. Methods Enzymol. 115, 157–171 (1985).

    Article  CAS  Google Scholar 

  20. Jones, T. A., Zhou, J., Cowan, S. W. & Kjeldgaard, M. Acta crystallogr. A47, 110–119 (1992).

    Google Scholar 

  21. Brünger, A. T. X-PLOR Manual Version 3.1 (Yale Univ. Press, New Haven, CT, 1992).

    Google Scholar 

  22. Engh, R. A. & Huber, R. Acta crystallogr. A57, 392–400 (1991).

    Article  Google Scholar 

  23. Parkinson, G., Vojtechovsky, J., Clowney, L., Brünger, A. T. & Berman, H. M. Acta crystallogr. D52, 57–64 (1996).

    CAS  Google Scholar 

  24. Brünger, A. T., Krokowski, A. & Erickson, J. W. Acta crystallogr. A46, 585–593 (1990).

    Article  Google Scholar 

  25. Ramachandran, G. N. & Sasiekharan, V. Adv. Protein Chem. 23, 283–438 (1968).

    Article  CAS  Google Scholar 

  26. Babcock, M. S. & Olson, W. K. J. molec. Biol. 237, 98–124 (1994).

    Article  CAS  Google Scholar 

  27. Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K. & Pease, L. R. Gene 77, 51–59 (1989).

    Article  CAS  Google Scholar 

Download references

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Author notes

  1. Michael Klemsz

    Present address: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, 46202-5120, USA

Authors and Affiliations

  1. La Jolla Cancer Research Center at The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California, 92037, USA

    Ramadurgam Kodandapani, Frédéric Pio, Chao-Zhou Ni, Scott McKercher, Richard A. Maki & Kathryn R. Ely

  2. Dipartimento di Chimica Organica e Biologica, Universita degli Studi di Napoli Federico II, 80134, Napoli, Italy

    Gennaro Piccialli

  3. Neurocrine Biosciences, San Diego, California, 92121, USA

    Richard A. Maki

Authors
  1. Ramadurgam Kodandapani
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  2. Frédéric Pio
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  3. Chao-Zhou Ni
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  4. Gennaro Piccialli
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  5. Michael Klemsz
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  6. Scott McKercher
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  7. Richard A. Maki
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  8. Kathryn R. Ely
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Kodandapani, R., Pio, F., Ni, CZ. et al. A new pattern for helix–turn–helix recognition revealed by the PU.l ETS–domain–DNA complex. Nature 380, 456–460 (1996). https://doi.org/10.1038/380456a0

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