Article | Published:

Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA

Naturevolume 352pages497505 (1991) | Download Citation

Subjects

Abstract

Two crystal structures of the glucocorticoid receptor DNA-binding domain complexed with DNA are reported. The domain has a globular fold which contains two Zn-nucleated substructures of distinct conformation and function. When it binds DNA, the domain dimerizes, placing the subunits in adjacent major grooves. In one complex, the DNA has the symmetrical consensus target sequence; in the second, the central spacing between the target's half-sites is larger by one base pair. This results in one subunit interacting specifically with the consensus target half-site and the other nonspecifically with a noncognate element. The DNA-induced dimer fixes the separation of the subunits' recognition surfaces so that the spacing between the half-sites becomes a critical feature of the target sequence's identity.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Chandler, V. L., Maler, B. A. & Yamamoto, K. R. Cell 33, 489–499 (1983).

  2. 2

    Ponta, H., Kennedy, N., Skroch, P., Hynes, N. E. & Groner, B. Proc. natn. Acad. Sci. U.S.A. 82, 1020–1024 (1985).

  3. 3

    Issemann, I. & Green, S. Nature 347, 645–649 (1990).

  4. 4

    Beato, M. Cell 56, 335–344 (1988).

  5. 5

    Evans, R. M. Science 242, 889–895 (1988).

  6. 6

    Nauber, U. et al. Nature 336, 489–492 (1988).

  7. 7

    Segraves, W. A. & Hogness, D. S. Genes Dev. 4, 204–219 (1990).

  8. 8

    Wang, L-H. et al. Nature 340, 163–166 (1989).

  9. 9

    Danielson, M., Hinck, L. & Ringold, G. M. Cell 57, 1131–1138 (1989).

  10. 10

    Mader, S., Kumar, V., de Verneuil, H. & Chambon, P. Nature 338, 271–274 (1989).

  11. 11

    Umesono, K. & Evans, R. M. Cell 57, 1139–1146 (1989).

  12. 12

    Green, S., Kumar, V., Theulaz, I., Wahli, W. & Chambon, P. EMBO J. 7, 3037–3044 (1988).

  13. 13

    Freedman, L. P. et al. Nature 334, 543–546 (1988).

  14. 14

    Miller, J., McLachlan, A. D. & Klug, A. EMBO J. 4, 1609–1614 (1985).

  15. 15

    Brown, R. S., Sander, C. & Argos, P. FEBS Lett. 186, 274–274 (1985).

  16. 16

    Berg, J. Proc. natn. Acad. Sci. U.S.A. 85, 99–102 (1988).

  17. 17

    Klug, A. & Rhodes, D. Trends biol. Sci. 12, 464–469 (1987).

  18. 18

    Klevit, R. E., Herriott, J. R. & Horvath, S. J. Proteins 7, 215–226 (1990).

  19. 19

    Lee, M. S., Gippert, G. P., Soman, K. V., Case, D. A. & Wright, P. E. Science 245, 635–637 (1989).

  20. 20

    Hard, T. et al. Science 249, 157–160 (1990).

  21. 21

    Schwabe, J. W. R., Neuhaus, D. & Rhodes, D. Nature 348, 458–461 (1990).

  22. 22

    Pavletich, N. P. & Pabo, C. O. Science 252, 809–817 (1991).

  23. 23

    Klock, G., Strahle, U. & Schutz, G. Nature 329, 734–736 (1987).

  24. 24

    Freedman, L., Yamamoto, K., Luisi, B. F. & Sigler, P. Cell, 54, 444 (1988).

  25. 25

    Tsai, S. Y. et al. Cell 55, 361–369 (1988).

  26. 26

    Hard, T., Dahlman, K., Carlstedt-Duke, J., Gustaffson, J.-A. & Rigler, R. Biochemistry 29, 5358–5364 (1990).

  27. 27

    Schevitz, R. W., Podjarny, A. D., Zwick, M., Hughes, J. J. & Sigler, P. B. Acta crystallogr. A37, 669–677 (1981).

  28. 28

    Wang, B.-C., Meth. Enzym. 115, 90–112 (1985).

  29. 29

    Finzel, B. C. J. appl. Crystallogr. 20, 53–57 (1987).

  30. 30

    Westof, E., Dumas, P. & Moras, D. J. molec. Biol. 184, 119–145 (1985).

  31. 31

    Hendrickson, W. A. & Konnert, J. H. in Structure, Conformation, Function and Evolution Vol. 1 (ed. Srinivasa, R.) 43–57 (1981).

  32. 32

    Otwinowski, Z. et al. Nature 335, 321–329 (1988).

  33. 33

    Brunger, A. Crystallographic Computing 4: Techniques and New Technologies (ed. Isaacs, N. W. & Taylor, M. R.) (Oxford University Press, 1988).

  34. 34

    Saenger, W. Principles of Nucleic Acid Structure 120 (Springer-Verlag, New York, 1984).

  35. 35

    Somers, W. A. thesis, Univ, Leeds, UK (1991).

  36. 36

    Schultz, S. & Steitz, T. A. Science (in the press).

  37. 37

    Schena, M., Freedman, L. P. & Yamamoto, K. R. Genes Dev. 3, 1590–1601 (1989).

  38. 38

    Severne, Y., Wieland, S., Schaffner, W. & Rusconi, S. EMBRO J. 7, 2503–2508 (1988).

  39. 39

    Summers, M. F., South, T. L., Kim, B. & Hare, D. R. Biochemistry 29, 329–340 (1990).

  40. 40

    Picard, D. & Yamamoto, K. R. EMBO J. 6, 3333–3340 (1987).

  41. 41

    Scheidereit, C. & Beato, M. Proc. natn. Acad. Sci. U.S.A. 81, 3029–3033 (1984).

  42. 42

    Scheidereit, C., Westphal, H. M., Carlson, C., Bosshard, H. & Beato, M. DNA 5, 383–391 (1986).

  43. 43

    Forman, B. M. & Samuels, H. H. Molec. Endocrin. 4, 1293–1301 (1990).

  44. 44

    Hughes, M. R. et al. Science 242, 1702–1705 (1988).

  45. 45

    Rhodes, D. & Klug, A. Nature 286, 573–578 (1980).

  46. 46

    Dahlman-Wright, K., Wright, A., Gustafsson, J.-A. & Carlstedt-Duke, J. J. biol. Chem. 266, 3107–3112 (1991).

  47. 47

    Dahlman-Wright, K., Siltala-Roos, H., Carlstedt-Duke, J. & Gustafsson, J.-A. J. biol. Chem. 265, 14030–14035 (1990).

  48. 48

    Jantzen, H.-M. et al. Cell 49, 29–38 (1987).

  49. 49

    Sakai, D. D. et al. Genes Dev. 2, 1144–1154 (1988).

  50. 50

    Diamond, M. I., Miner, J. N., Yoshinaga, S. K. & Yamamoto, K. R. Science 249, 1266–1272 (1990).

  51. 51

    Zhang, R.-G. et al. Nature 327, 591–597 (1987).

  52. 52

    Kissinger, C. R., Liu, B., Martin-Bianco, E., Kornberg, T. B. & Pabo, C. O. Cell 63, 579–590 (1990).

  53. 53

    Read, R. J. Acta crystallogr. A42, 140–149 (1986).

  54. 54

    Presley, J. P. J. appl. Crystallogr. 21, 572–576 (1988).

  55. 55

    Richmond, T. J., Finch, J. T., Rushton, B., Rhodes, D. & Klug, A. Nature 311, 532–536 (1984).

Download references

Author information

Author notes

    • B. F. Luisi

    Present address: MRC Virology Unit, Institute of Virology, Church Street, Glasgow, G115JT, UK

    • L. P. Freedman

    Present address: Cell Biology and Genetics Program, Sloan-Kettering Institute, 1275 York Avenue, New York, 10021, USA

Affiliations

  1. Department of Molecular Biophysics and Biochemistry, and the Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, 06511, USA

    • B. F. Luisi
    • , W. X. Xu
    • , Z. Otwinowski
    •  & P. B. Sigler
  2. Department of Biochemistry and Biophysics, University of California, San Francisco, California, 94143-0448, USA

    • L. P. Freedman
    •  & K. R. Yamamoto

Authors

  1. Search for B. F. Luisi in:

  2. Search for W. X. Xu in:

  3. Search for Z. Otwinowski in:

  4. Search for L. P. Freedman in:

  5. Search for K. R. Yamamoto in:

  6. Search for P. B. Sigler in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/352497a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.