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The TEAD4–YAP/TAZ Protein–Protein Interaction: Expected Similarities and Unexpected Differences
Author(s) -
Hau Jean Christophe,
Erdmann Dirk,
Mesrouze Yannick,
Furet Pascal,
Fontana Patrizia,
Zimmermann Catherine,
Schmelzle Tobias,
Hofmann Francesco,
Chène Patrick
Publication year - 2013
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300163
Subject(s) - hippo signaling pathway , transcription factor , biology , structural similarity , computational biology , plasma protein binding , microbiology and biotechnology , binding site , affinities , dna binding protein , protein structure , genetics , gene , effector , biochemistry
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.