BBB seminar: Gilles Travé
Structural studies on the E6 human papillomavirus oncoprotein responsible for cervical cancer
CNRS, Ecole Supérieure de Biotechnologie Strasbourg, Illkirch, France and
Professor II at the Department of Molecular Biology, University of Bergen
Cervical cancers are caused by “high risk” human papilloma viruses (HPVs). More than 100 types of human papillomavirus types have been isolated and their DNA sequenced. They vary much in terms of tropism, associated illnesses, and oncogenicity. "High risk" HPVs generate cancer via two oncoproteins, E6 and E7. E6 oncogenicity seems related to its ability to mediate interactions between the tumor suppressor protein p53 and the ubiquitin-ligase E6-AP, effectively leading to p53 degradation. In addition, E6 binds to many other cellular proteins or domains, in particular to a family of PDZ domains. E6 also recognizes DNA structures found in Holliday junctions. E6 is a small cystein-rich protein of 158 residues consisting of two zinc binding domains (E6-N and E6-C). Structural data on this protein have remained sparse due to problems imposed by the production of recombinant E6. Protein quality optimization strategies have allowed us to obtain monodisperse samples of a folded HPV16 E6 mutant with preserved wild-type properties. We have recently solved by NMR the solution structure of the C-terminal half of E6. The talk will describe the structure and its implications in terms of E6 activities: p53 binding and degradation, recognition of PDZ domains, DNA junction binding. We will also combine the structural data and protein alignments to discuss the similarities and differences between E6 protein issues from different HPV groups.
Gilles Travé's main research interests are the structural aspects of proteins (folding, stability, conformational changes, interactions) and their biological properties.
Gilles is from the wine-village Banyuls, near Perpignan in the South of France. He was educated as a Chemistry Engineer and obtained a PhD in Biochemistry/Molecular Biology from Toulouse and Montpellier. Supervised by Jean-Pierre Liautard, he analysed the biochemical and bio-physical properties of annexin I, a calcium-dependent lipid-binding protein. He also performed studies on muscle/cytoskeletal proteins such as spectrin and tropomyosin, and designed peptides which inhibit HIV infection of human T-cells by blocking the CD4-gp120 interaction.
From 1992 to 1994, Gilles did his post-doctoral work at the EMBL (Heidelberg, Germany) with Annalisa Pastore (NMR structure of protein modules) and Matti Saraste (biochemical and structural characterisation of protein modules). During this period, he solved the structures of the C-terminal EF-hands of human spectrin in the presence and absence of calcium.
In 1995 he became a Research Associate at The French National Center for Scientific Research (CNRS) in the NMR group of the “Ecole Supérieure de Biotechnologie de Strasbourg” where he ever since has been working on the structure-function analysis of the human papillomavirus (HPV) E6 oncoprotein. This work involves basic studies on heterologous expression of recombinant proteins and the analysis of the monodispersity and quality of such proteins.
In 2003 Gilles was appointed Professor II at the Department of Molecular Biology, University of Bergen.