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The TEAD4-YAP/TAZ protein-protein interaction: expected similarities and unexpected differences

Hau, Jean-Christophe, Erdmann, Dirk, Mesrouze, Yannick, Furet, Pascal, Fontana, Patrizia, Zimmermann, Catherine, Schmelzle, Tobias, Hofmann, Francesco and Chene, Patrick (2013) The TEAD4-YAP/TAZ protein-protein interaction: expected similarities and unexpected differences. ChemBioChem, 14 (10). pp. 1218-1225. ISSN 1439-4227


The Hippo pathway controls cell homeostasis, and its deregulation can lead to human diseases. Within this pathway, the YAP and TAZ transcriptional cofactors hold a key role in stimulating gene transcription via their interaction with the TEAD transcriptional factors. Our study of YAP and TAZ peptides in biochemical and biophysical assays shows that both proteins have the same affinity for TEAD. Molecular modeling and structural biology data suggest that they also bind to the same site on TEAD. However, this apparent similarity hides differences in the way both proteins interact with TEAD. The secondary structure elements of their TEAD-binding site do not contribute equally to the overall affinity, and critical interactions with TEAD are made by different residues. This convergent optimization of the YAP/TAZ TEAD-binding site suggests that binding of YAP and TAZ with similar affinity to TEAD is important for Hippo pathway functionality

Item Type: Article
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Keywords: protein-protein interaction, Yap, Hippo, TEAD, peptide, molecular recognition
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Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13