Virtually every biological process involves the interaction between proteins. The structural diversity and the number of protein-protein interfaces (PPIs) offer an enormous number of potential drug targets. Our research in the area of molecular recognition aims to enhance our understanding of PPIs and eventually contribute knowledge toward identification of drug targets. We have in the past studied different PPIs (e.g., p53-hdm2), and our work in this area contributed to the identification and development of compounds that are currently in the clinic. We would like to expand our knowledge in the PPI field, using as a model the YAP-TEAD interaction. This PPI is attractive for drug discovery because inhibitors of the YAP-TEAD interaction might be new anticancer drugs. In addition, the YAP-TEAD interaction is a very nice model in molecular recognition to carry out fundamental studies on PPIs in areas such as intrinsically-disordered proteins, cooperative binding, and transition state mapping. We have recently developed several biochemical techniques to study the YAP-TEAD interaction, and we plan to perform pre-steady state measurements with stopped flow, which should help elucidate the different molecular events taking place during the interaction between the transcription factor TEAD and its coactivators. The knowledge gained from these studies could be combined with cellular work (e.g., using protein mutants in cells) and should help enhance our understanding of these interactions in order to guide our drug discovery activities.
The surprising features of the TEAD4-Vgll1 protein-protein interaction.
Mesrouze Y, Hau JC, Erdmann D, Zimmermann C, Fontana P, Schmelzle T, Chène P.
Chembiochem. 2014 Mar 3;15(4):537-42.
The TEAD4-YAP/TAZ protein-protein interaction: expected similarities and unexpected differences.
Hau JC, Erdmann D, Mesrouze Y, Furet P, Fontana P, Zimmermann C, Schmelzle T, Hofmann F, Chène P.
Chembiochem. 2013 Jul 8;14(10):1218-25.
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