Original Article

Oncogene (2006) 25, 5953–5959. doi:10.1038/sj.onc.1209584; published online 24 April 2006

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

O Ohlenschläger1, T Seiboth1, H Zengerling1, L Briese1,4, A Marchanka1, R Ramachandran1, M Baum1, M Korbas2, W Meyer-Klaucke2, M Dürst3 and M Görlach1

  1. 1Fritz-Lipmann-Institut, Jena, Germany
  2. 2EMBL Hamburg/DESY, Hamburg, Germany
  3. 3Frauenklinik der Friedrich-Schiller-Universität, Jena, Germany

Correspondence: Dr M Görlach, Molecular Biophysics/NMR Spectroscopy, Fritz-Lipmann-Institut, Beutenbergstr. 11, D-07745 Jena, Germany. E-mail: mago@fli-leibniz.de

4Current address: General Electrics, Munzinger Str. 9, D-79111 Freiburg, Germany.

Received 9 January 2006; Revised 3 March 2006; Accepted 8 March 2006; Published online 24 April 2006.



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 beta1beta2alpha1beta3alpha2 topology representing a unique zinc-binding fold found only for E7. Dimerization occurs through the alpha1/alpha1' helices and intermolecular beta-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 alpha1 and beta1 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.


human papilloma virus, E7, carcinogenesis, NMR solution structure