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.
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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.
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Ohlenschläger, O., Seiboth, T., Zengerling, H. et al. Solution structure of the partially folded high-risk human papilloma virus 45 oncoprotein E7. Oncogene 25, 5953–5959 (2006). https://doi.org/10.1038/sj.onc.1209584
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DOI: https://doi.org/10.1038/sj.onc.1209584
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