Crystal structure of the human papillomavirus type 18 E2 activation domain

The papillomavirus E2 protein regulates viral transcription and DNA replica tion through interactions with cellular and viral proteins. The amino-termi nal activation domain, which represents a protein class whose structural th emes are poorly understood, contains key residues that mediate these functi onal contacts, The crystal structure of a protease-resistant core of the hu man papillomavirus type 18 E2 activation domain reveals a novel fold creati ng a cashew-shaped form with a glutamine-rich alpha helix packed against a beta-sheet framework. The protein surface shows extensive overlap of determ inants for replication and transcription. The structure broadens the concep t of activators to include proteins with potentially malleable, but certain ly ordered, structures.