Abstract
Papillomaviruses cause warts and proliferative lesions in skin and other epithelia. In a minority of papillomavirus types (‘high risk’, including human papillomaviruses 16, 18, 31, 33, 45 and 56), further transformation of the wart lesions can produce tumours1. The papillomavirus E2 protein controls primary transcription and replication of the viral genome2. Both activities are governed by a ∼200 amino-acid amino-terminal module (E2NT) which is connected to a DNA-binding carboxy-terminal module by a flexible linker. Here we describe the crystal structure of the complete E2NT module from human papillomavirus 16. The E2NT module forms a dimer both in the crystal and in solution. Amino acids that are necessary for transactivation are located at the dimer interface, indicating that the dimer structure may be important in the interactions of E2NT with viral and cellular transcription factors. We propose that dimer formation may contribute to the stabilization of DNA loops3 which may serve to relocate distal DNA-binding transcription factors to the site of human papillomavirus transcription initiation.
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Acknowledgements
K.S.W., G.G.D., A.A.A and O.V.M. thank the BBSRC for infrastructure support and the EC for supporting work at EMBL, Hamburg, through the Access to Large Installations Project, Contract Number CHGE-CT93-0040. We also thank Yorkshire Cancer Research for project and program grant support to N.J.M., J.E.B., I.B.B. and O.V.M. A.A.A. is supported by a Wellcome Trust Career Development Fellowship.
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Antson, A., Burns, J., Moroz, O. et al. Structure of the intact transactivation domain of the human papillomavirus E2 protein. Nature 403, 805–809 (2000). https://doi.org/10.1038/35001638
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DOI: https://doi.org/10.1038/35001638
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