Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli

Abstract

Examination of the structure of Escherichia coli heat-labile enterotoxin in the AB5 complex at a resolution of 2.3 Å reveals that the doughnut-shaped B pentamer binds the enzymatic A subunit using a hairpin of the A2 fragment, through a highly charged central pore. Putative ganglioside GM1-binding sites on the B subunits are more than 20 Å removed from the membrane-crossing Al subunit. This ADP-ribosylating (Al) fragment of the toxin has structural homology with the catalytic region of exotoxin A and hence also to diphtheria toxin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Foster, J. W. & Kinney, D. M. CRC crit. Rev. Microbiol. 11, 273–298 (1985).

    Article  CAS  Google Scholar 

  2. Moss, J. & Vaughan, M. Adv. Enzym. 61, 303–379 (1988).

    CAS  Google Scholar 

  3. van Heyningen, S. in Current Topics in Membranes and Transport Vol. 18, 445–471 (Academic, New York, 1983).

    Google Scholar 

  4. Finkelstein, R. A. in Immunochemical and Molecular Genetic Analysis of Bacterial Pathogens (eds Owen, P. & Foster, T. J.) 85–102 (Elsevier New York, 1988).

    Google Scholar 

  5. Geary, S. J., Marchlewicz, B. A. & Finkelstein, R. A. Infect. Immunity 36, 215–220 (1982).

    CAS  Google Scholar 

  6. Dallas, W. S. & Falkow, S. Nature 288, 499–501 (1980).

    Article  ADS  CAS  Google Scholar 

  7. Yamamoto, T., Gojobori, T. & Yokota, T. J. Bact. 169, 1352–1357 (1987).

    Article  CAS  Google Scholar 

  8. Hirst, T. R., Sanchez, J., Kaper, J. B., Hardy, S. J. S. & Holmgren, J. Proc. natn. Acad. Sci. U.S.A. 81, 7752–7756 (1984).

    Article  ADS  CAS  Google Scholar 

  9. Hofstra, H. & Witholt, B. J. biol. Chem. 259, 15182–15187 (1984).

    CAS  PubMed  Google Scholar 

  10. Spicer, E. K. & Noble, J. A. J. biol. Chem. 257, 5716–5721 (1982).

    CAS  PubMed  Google Scholar 

  11. Mekalanos, J. J., Collier, R. J. & Romig, W. R. J. biol. Chem. 254, 5855–5861 (1979).

    CAS  PubMed  Google Scholar 

  12. Moss, J., Osborne, J. C. Jr. Fishman, P. H., Nakaya, S. & Robertson, D. C. J. biol. Chem. 256, 12861–12865 (1981).

    CAS  PubMed  Google Scholar 

  13. Gill, D. M. Biochemistry 15, 1242–1248 (1976).

    Article  CAS  Google Scholar 

  14. Gill, D. M. & Richardson, S. H. J. infect. Dis. 141, 64–70 (1980).

    Article  CAS  Google Scholar 

  15. Cassel, D. & Pfeuffer, T. Proc. natn. Acad. Sci. U.S.A. 75, 2669–2673 (1978).

    Article  ADS  CAS  Google Scholar 

  16. Moss, J. & Vaughan, M. J. biol. Chem. 252, 2455–2457 (1977).

    CAS  PubMed  Google Scholar 

  17. Kahn, R. A. & Gilman, A. G. J. biol. Chem. 261, 7906–7911 (1986).

    CAS  PubMed  Google Scholar 

  18. Gill, D. M. & Coburn, J. Biochemistry 26, 6364–6371 (1987).

    Article  CAS  Google Scholar 

  19. Peterson, J. W. & Ochoa, L. G. Science 245, 857–859 (1989).

    Article  ADS  CAS  Google Scholar 

  20. Mekalanos, J. J. et al. Nature 306, 551–557 (1983).

    Article  ADS  CAS  Google Scholar 

  21. Clemens, J. D. et al. Lancet II, 124–127 (1986).

    Article  Google Scholar 

  22. Schödel, F. & Will, H. Infect. Immunity 57, 1347–1350 (1989).

    Google Scholar 

  23. Sanchez, J., Svennerholm, A.-M. & Holmgren, J. FEBS Lett. 241, 110–114 (1988).

    Article  CAS  Google Scholar 

  24. Dertzbaugh, M. T., Peterson, D. L. & Macrina, F. L. Infect. Immunity 58, 70–79 (1990).

    CAS  Google Scholar 

  25. Czerknsky, C., Russell, M. W., Lycke, N., Lindblad, M. & Holmgren, J. Infect. Immunity 57, 1072–1077 (1989).

    Google Scholar 

  26. Fujinaga, M., Gros, P. & van Gunsteren, W. F. J. appl. Crystallogr. 22, 1–8 (1989).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  28. Ladenstein, R. et al. J. molec. Biol. 203, 1045–1070 (1988).

    Article  CAS  Google Scholar 

  29. Jacob, C. O., Leitner, M., Zamir, A., Salomon, D. & Arnon, R. EMBO J. 4, 3339–3343 (1985).

    Article  CAS  Google Scholar 

  30. lida, T. et al. J. biol. Chem. 264, 14065–14070 (1989).

    Google Scholar 

  31. Kabsch, W. & Sander, C. Biopolymers 22, 2577–2637 (1983).

    Article  CAS  Google Scholar 

  32. Janin, J., Miller, S. & Chothia, C. J. molec. Biol. 204, 155–164 (1988).

    Article  CAS  Google Scholar 

  33. Goins, B. & Freire, E. Biochemistry 27, 2046–2052 (1988).

    Article  CAS  Google Scholar 

  34. De Wolf, M. J. S., Fridkin, M. & Kohn, L. D. J. biol. Chem. 256, 5489–5496 (1981).

    CAS  PubMed  Google Scholar 

  35. Ludwig, D. S., Holmes, R. K. & Schoolnik, G. K. J. biol. Chem. 260, 12528–12534 (1985).

    CAS  PubMed  Google Scholar 

  36. Tsuji, T., Honda, T., Miwatani, T., Wakabayashi, S. & Matsubara, H. J. biol Chem. 260, 8552–8558 (1985).

    CAS  PubMed  Google Scholar 

  37. Montfort, W. et al. J. biol. Chem. 262, 5398–5403 (1987).

    CAS  PubMed  Google Scholar 

  38. Tomasi, M. & Montecucco, C. J. biol. Chem. 256, 11177–11181 (1981).

    CAS  PubMed  Google Scholar 

  39. Wisnieski, B. J. & Bramhall, J. S. Nature 289, 319–321 (1981).

    Article  ADS  CAS  Google Scholar 

  40. Surewicz, W. K., Leddy, J. J. & Mantsch, H. H., Biochemistry 29, 8106–8111 (1990).

    Article  CAS  Google Scholar 

  41. Dwyer, J. D. & Bloomfield, V. A. Biochemistry 21, 3227–3231 (1982).

    Article  CAS  Google Scholar 

  42. Ribi, H. O., Ludwig, D. S., Mercer, K. L., Schoolnik, G. K. & Kornberg, R. D. Science 239, 1272–1276 (1988).

    Article  ADS  CAS  Google Scholar 

  43. McDaniel, R. V. & Mclntosh, T. J. Biophys. J. 49, 94–96 (1986).

    Article  ADS  CAS  Google Scholar 

  44. Allured, V. S., Collier, R. J., Carroll, S. F. & McKay, D. B. Proc. natn. Acad. Sci. U.S.A. 83, 1320–1324 (1986).

    Article  ADS  CAS  Google Scholar 

  45. Brandhuber, B. J., Allured, V. S., Falbel, T. G. & McKay, D. B. Proteins 3, 146–154 (1988).

    Article  CAS  Google Scholar 

  46. Carroll, S. F. & Collier, R. J. J. biol. Chem. 262, 8707–8711 (1987).

    CAS  PubMed  Google Scholar 

  47. Douglas, C. M. & Collier, R. J. J. Bact. 169, 4967–4971 (1987).

    Article  CAS  Google Scholar 

  48. Tsuji, T. et al. J. biol. Chem. 265, 22520–22525 (1990).

    CAS  PubMed  Google Scholar 

  49. Harford, S., Dykes, C. W., Hobden, A. N., Read, M. J. & Halliday, I. J. Eur. J. Biochem. 183, 311–316 (1989).

    Article  CAS  Google Scholar 

  50. Lai, C.-Y., Xia, Q.-C. & Salotra, P. T. Biochem. biophys. Res. Commun. 116, 341–348 (1983).

    Article  CAS  Google Scholar 

  51. Okamoto, K. et al. J. Bact. 170, 2208–2211 (1988).

    Article  CAS  Google Scholar 

  52. Lukac, M. & Collier, R. J. Biochemistry 27, 7629–7632 (1988).

    Article  CAS  Google Scholar 

  53. Galloway, T. S. & van Heyningen, S. Biochem. J. 244, 225–230 (1987).

    Article  CAS  Google Scholar 

  54. Pickett, C. L., Twiddy, E. M., Coker, C. & Holmes, P. K. J. Bact. 171, 4945–4952 (1989).

    Article  CAS  Google Scholar 

  55. Pronk, S. E. et al. J. biol. Chem. 260, 13580–13584 (1985).

    CAS  PubMed  Google Scholar 

  56. Messerschmidt, A. & Pflugrath, J. W. J. appl. Crystallogr. 20, 306–315 (1987).

    Article  CAS  Google Scholar 

  57. Kabsch, W. J. appl. Crystallogr. 21, 916–924 (1988).

    Article  CAS  Google Scholar 

  58. Leslie, A. G. W. Acta crystallogr. A43, 134–136 (1987).

    Article  CAS  Google Scholar 

  59. Jones, T. A. J. appl. Crystallogr. 11, 268–272 (1978).

    Article  CAS  Google Scholar 

  60. Jones, T. A. & Thirup, S. EMBO J. 5, 819–822 (1986).

    Article  CAS  Google Scholar 

  61. Tronrud, D. E., Ten Eyck, L. F. & Matthews, B. W. Acta crystallogr. A43, 489–501 (1987).

    Article  Google Scholar 

  62. Sandkvist, M., Hirst, T. R. & Bagdasarian, M. J. Bact. 169, 4570–4576 (1987).

    Article  CAS  Google Scholar 

  63. Gray, G. L. et al. Proc. natn. Acad. Sci. U.S.A. 81, 2645–2649 (1984).

    Article  ADS  CAS  Google Scholar 

  64. Greenfield, L. et al. Proc. natn. Acad. Sci. U.s.a. 80, 6853–6857 (1983).

    Article  ADS  CAS  Google Scholar 

  65. Ratti, G., Rappouloli, R. & Giannini, G. Nucleic Acids Res. 11, 6589–6595 (1983).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sixma, T., Pronk, S., Kalk, K. et al. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Nature 351, 371–377 (1991). https://doi.org/10.1038/351371a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/351371a0

This article is cited by

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.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing