Structure of the intact transactivation domain of the human papillomavirusE2 protein

Papillomaviruses cause warts and proliferative lesions in skin and other ep ithelia. In a minority of papillomavirus types ('high risk'. including huma n papillomaviruses 16, 18, 31, 33, 45 and 56), further transformation of th e wart lesions can produce tumours'. The papillomavirus E2 protein controls primary transcription and replication of the viral genome(2). Both activit ies are governed by a similar to 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 cr ystal and in solution. Amino acids that are necessary for transactivation a re located at the dimer interface, indicating that the dimer structure may be important in the interactions of E2NT with viral and cellular transcript ion factors. We propose that dimer formation may contribute to the stabiliz ation of DNA loops(3) which may serve to relocate distal DNA-binding transc ription factors to the site of human papillomavirus transcription initiatio n.