Papillomaviruses cause epithelial tumors including cervical cancer, which is a leading cause of cancer deaths in women and is an AIDS-associated malignancy. The papillomavirus E6 oncoprotein plays a critical role in virus replication and is essential in the development of cervical cancer. A molecular structure of E6 is critical for the design of therapeutic strategies. Unfortunately, elucidating the structure of the E6 protein has remained elusive for decades because the physical properties of E6 have frustrated structural studies. This application has overcome these difficulties and will solve the solution structure of E6 by NMR techniques. The structural features of E6 at the atomic level will be correlated to its multiple biological functions. PUBLIC HEALTH RELEVANCE: Papillomaviruses cause numerous cancers, including cervical cancer, because they make a protein called E6 that helps make normal cells into cancerous cells. Understanding the atomic structure of E6 will aid our understanding of how E6 works, and could lead to drugs that act against E6 and thereby against cervical cancer. This application will solve the atomic structure of E6 and perform experiments to show how the E6 structure participates in causing cancer.