The TEAD4–YAP/TAZ Protein–Protein Interaction: Expected Similarities and Unexpected Differences. Issue 10 (18th June 2013)

• Record Type: Journal Article
• Authors: Hau, Jean Christophe; Erdmann, Dirk; Mesrouze, Yannick; Furet, Pascal; Fontana, Patrizia; Zimmermann, Catherine; Schmelzle, Tobias; Hofmann, Francesco; Chène, Patrick
• Is Part Of: Chembiochem. Volume 14:Issue 10(2013)
• Page Start: 1218
• Page End: 1225
• Publication Date: 2013-06-18
• Subjects: Hippo pathway -- omega loops -- peptides -- protein–protein interactions -- TAZ -- TEAD -- YAP; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300163
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: The Hippo pathway controls cell homeostasis, and its deregulation can lead to human diseases. In this pathway, the YAP and TAZ transcriptional cofactors play a key role in stimulating gene transcription through their interaction with the TEAD transcriptional factors. Our study of YAP and TAZ peptides in biochemical and biophysical assays shows that both proteins have essentially 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 ways in which the two 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 through different residues. This convergent optimization of the YAP/TAZ TEAD binding site suggests that the similarity in the affinities of binding of YAP to TEAD and of TAZ to TEAD is important for Hippo pathway functionality. Abstract : Hippo pathway functionality : YAP and TAZ are two homologous cofactors that bind with similar affinities to the same binding site on the surface of the TEAD transcription factor, and this might be important for Hippo pathway functionality. However, there are several molecular differences between the binding of YAP and TAZ to TEAD.