Original Article

Solution structure of the partially folded high-risk human papilloma virus 45 oncoprotein E7

  • Oncogene 25, 59535959 (28 September 2006)
  • doi:10.1038/sj.onc.1209584
  • Download Citation
Received:
Revised:
Accepted:
Published online:

Abstract

The oncoprotein E7 of human papilloma viruses (HPV) is involved in the pathogenesis and maintenance of human cervical cancers. The most prevalent HPV types found in cervix carcinomas are HPV16, 18 and 45. The structure of the E7 dimer from HPV45 (PDB 2F8B) was determined by nuclear magnetic resonance spectroscopy. Each monomer comprises an unfolded N-terminus and a well-structured C-terminal domain with a β1β2α1β3α2 topology representing a unique zinc-binding fold found only for E7. Dimerization occurs through the α1/α1′ helices and intermolecular β-sheet formation but excludes the zinc-binding sites. E7 is reported to interact with a number of cellular proteins (e.g. pRb, p21CIP1). Binding of a peptide derived from the C-terminus of p21CIP1 to the C-terminal domain of E7 was characterized by monitoring chemical shift perturbations of the amide groups of E7. This provides direct evidence that a shallow groove situated between α1 and β1 of the E7 C-terminal domain is interacting with the C-terminus of p21CIP1. Intriguingly, this binding site overlaps with the low-affinity binding site on E7 for the C-domain of pRb.

  • Subscribe to Oncogene for full access:

    $2190

    Subscribe

Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

References

  1. , , , , , et al. (2002). Biochemistry 41: 10510–10518.

  2. , , . (2003). Oncogene 22: 3833–3841.

  3. , , , , , . (1990). EMBO J 9: 153–160.

  4. , , . (1989). J Virol 63: 1404–1407.

  5. , , , , . (1995). J Biomol NMR 6: 1–10.

  6. , , . (1992). Biochemistry 31: 12117–12125.

  7. , , . (2005). Mol Cell Biol 25: 1013–1024.

  8. , . (2003). J Natl Cancer Inst Monogr 31: 3–13.

  9. , , , , , et al. (1998). Oncogene 16: 1085–1089.

  10. , , , , , et al. (1999). EMBO J 18: 2449–2458.

  11. , , , , . (2001). Nat Struct Biol 8: 833–837.

  12. , , , , . (2000). Biochemistry 39: 16033–16045.

  13. , , , , . (2004). Virology 324: 17–27.

  14. . (2000). Biochim Biophys Acta 1471: M43–M56.

  15. , . (2005). Nat Rev Mol Cell Biol 6: 197–208.

  16. , , , , , . (1997). Genes Dev 11: 2090–2100.

  17. , . (2000). Proc Natl Acad Sci USA 97: 12513–12518.

  18. , , , , . (1992). EMBO J 11: 3289–3295.

  19. , , , , . (1996). Cell 87: 297–306.

  20. , , , , . (1998). J Biomol NMR 12: 543–548.

  21. , , . (1997). J Mol Biol 273: 283–298.

  22. , , . (2002). J Virol 76: 10559–10568.

  23. , , . (2002). J Mol Biol 319: 209–227.

  24. , , . (1997). Genes Dev 11: 2101–2111.

  25. , , . (1996). J Mol Graph 14: 51–55.

  26. , , , , . (1996). Proc Natl Acad Sci USA 93: 11504–11509.

  27. , , , , . (1996). J Biomol NMR 8: 477–486.

  28. , , . (1998). Nature 391: 859–865.

  29. , , , . (2006). J Biol Chem 281: 578–586.

  30. , , , , , et al. (2000). Mol Cell Biol 20: 6483–6495.

  31. , , , . (1993). J Virol 67: 3142–3150.

  32. , , , , , et al. (2004). J Virol 78: 11451–11460.

  33. , , , , , et al. (2001). Oncogene 20: 7888–7898.

  34. , , , , . (1989). J Virol 63: 4417–4421.

  35. , , , , . (1992). J Virol 66: 2418–2427.

  36. , , , , , et al. (2002). J Mol Biol 318: 533–546.

  37. , , , . (2005). J Biol Chem 280: 37868–37876.

  38. . (1997). Adv Cancer Res 71: 321–341.

  39. , . (1993). J Am Chem Soc 115: 7772–7777.

  40. , , , , , et al. (2003). Proc Natl Acad Sci USA 100: 2363–2368.

  41. . (1996). Biochim Biophys Acta 1288: F55–F78.

  42. , , , , , . (1997). J Am Chem Soc 119: 6711–6721.

  43. , . (2000). Adv Cancer Res 78: 1–29.

Download references

Acknowledgements

We thank M Stoldt, FZ Jülich, for the acquisition of a NOESY spectrum at 800 MHz, S Mensch and H Schwalbe, University Frankfurt, for providing the p21CIP1 peptide, J Wöhnert for critically reading the manuscript and the support from the EC Research Infrastructure Action (RII3/CT/2004/5060008). The Fritz Lipmann Institute is financially supported by the State of Thuringia and the Federal Government of Germany.

Author information

Author notes

    • L Briese

    Current address: General Electrics, Munzinger Str. 9, D-79111 Freiburg, Germany.

Affiliations

  1. Fritz-Lipmann-Institut, Jena, Germany

    • O Ohlenschläger
    • , T Seiboth
    • , H Zengerling
    • , L Briese
    • , A Marchanka
    • , R Ramachandran
    • , M Baum
    •  & M Görlach
  2. EMBL Hamburg/DESY, Hamburg, Germany

    • M Korbas
    •  & W Meyer-Klaucke
  3. Frauenklinik der Friedrich-Schiller-Universität, Jena, Germany

    • M Dürst

Authors

  1. Search for O Ohlenschläger in:

  2. Search for T Seiboth in:

  3. Search for H Zengerling in:

  4. Search for L Briese in:

  5. Search for A Marchanka in:

  6. Search for R Ramachandran in:

  7. Search for M Baum in:

  8. Search for M Korbas in:

  9. Search for W Meyer-Klaucke in:

  10. Search for M Dürst in:

  11. Search for M Görlach in:

Corresponding author

Correspondence to M Görlach.

Supplementary information

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).