A new team at the IGBMC
April 12, 2016
Last January, the IGBMC welcomed a new team leader: Gilles TRAVE and his coworkers Danièle ALTSCHUH, Yves NOMINE, and Irina Paula SUAREZ. We are all happy to receive this new team who will join the Department of Integrative Structural Biology. Its research theme will be: Viral Oncoproteins and Domain-motif networks.
To learn more about this team you can click on this link http://www.igbmc.fr/trave/. There is also a scientific news describing recent results of this team available by clicking on the button "More information".
The mystery lifted on viral mechanism of degradation of the protein p53 "guardian of the genome"
p53 proapoptotic tumor suppressor protein, is often called the "guardian of the genome" because of its key role in cancer prevention. Over 50% of human cancers contain mutations in the p53 gene, which result in defective proteins. Some viruses, such as HPV, the Polyoma virus and Adenovirus, favor the appearance of cancer by inactivating p53. In human papillomavirus (HPV) "high risk", responsible for cancers of the cervix, p53 is destroyed by the viral oncoprotein E6 that activates the cellular machinery for protein degradation.
In the first step of this process, E6 capture a cellular enzyme called E6AP. The E6 / E6AP resulting complex thereafter recruits p53. The E6AP enzyme then attaches on p53 a molecular biomarker, called ubiquitin, which will cause the destruction of p53 by the cellular machinery.
Researchers from the Laboratory Biotechnology and Cell Signaling (BCS), in collaboration with researchers from IGBMC have visualized at the atomic scale the first stage of p53 degradation. Using X-ray diffraction technique, they solved the three dimensional structure of a complex of the E6 protein of HPV 16 (the most prevalent HPV strain type), a small peptide fragment derived from E6AP, and the central region of the p53 protein. This structure shows how the small fragment of the E6AP protein leads E6 to adopt a particular form prone to interact with p53. Binding to E6AP shapes the overall conformation of E6 by generating on its surface a "pocket" which can accommodate p53.
The capture and degradation of p53 by E6 is a central activity of high-risk HPV, absolutely necessary for their propensity to cause cancer. Researchers at the BCS and IGBMC have described for the first time the E6-p53 targeting process at the atomic scale. These results provide a step forward in the design of therapeutic strategies to inhibit the degradation of p53.