Characterization of heterogeneous viral proteins by NMR methods: Human Adenovirus E1A and Human papillomavirus E7 proteins

HPV-16 E7 and HAdV-E1A proteins have been studied for years and despite documented attempts the characterization of these proteins either through NMR or X-ray crystallography failed due to their heterogeneous structural and dynamic properties. Thanks to the recently developed NMR approach to characterize highly heterogeneous proteins, in combination with clever sample preparation strategies, it was possible to complete the high resolution characterization through NMR of both, HPV16-E7 as well as HAdV-E1A. The information obtained, can now be used by the scientific community to answer the many open questions on the molecular determinants of the function of these two distinct proteins that are able to hijack cell regulation by a closely related mechanism. Indeed, the example of the high resolution study of one of the key post-translational modifications linked to the oncogenic process reported here just represents the first example of many studies that now can be performed taking advantage of the available NMR chemical shift assignment. This information can in turn be used to design innovative drugs that target, instead of well-structured proteins, these two IDPs.