The TEAD4-YAP/TAZ Protein-Protein Interaction: Expected Similarities and Unexpected Differences

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 peptide...

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Veröffentlicht in:Chembiochem : a European journal of chemical biology 2013-07, Vol.14 (10), p.1218-1225
Hauptverfasser: Hau, Jean Christophe, Erdmann, Dirk, Mesrouze, Yannick, Furet, Pascal, Fontana, Patrizia, Zimmermann, Catherine, Schmelzle, Tobias, Hofmann, Francesco, Chène, Patrick
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container_end_page 1225
container_issue 10
container_start_page 1218
container_title Chembiochem : a European journal of chemical biology
container_volume 14
creator Hau, Jean Christophe
Erdmann, Dirk
Mesrouze, Yannick
Furet, Pascal
Fontana, Patrizia
Zimmermann, Catherine
Schmelzle, Tobias
Hofmann, Francesco
Chène, Patrick
description 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. 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.
doi_str_mv 10.1002/cbic.201300163
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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. 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subjects Amino Acid Sequence
Animals
Binding sites
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Hippo pathway
Humans
Immunohistochemistry
Mice
Models, Molecular
Molecular Sequence Data
Muscle Proteins - chemistry
Muscle Proteins - genetics
Muscle Proteins - metabolism
Mutagenesis, Site-Directed
omega loops
peptides
Peptides - chemistry
Peptides - genetics
Peptides - metabolism
Protein Interaction Domains and Motifs
protein-protein interactions
Protein-Serine-Threonine Kinases - chemistry
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Proteins
Sequence Homology, Amino Acid
Signal Transduction
TAZ
TEAD
Transcription Factors - chemistry
Transcription Factors - genetics
Transcription Factors - metabolism
YAP
title The TEAD4-YAP/TAZ Protein-Protein Interaction: Expected Similarities and Unexpected Differences
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