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 |
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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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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.</description><identifier>ISSN: 1439-4227</identifier><identifier>EISSN: 1439-7633</identifier><identifier>DOI: 10.1002/cbic.201300163</identifier><identifier>PMID: 23780915</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>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</subject><ispartof>Chembiochem : a European journal of chemical biology, 2013-07, Vol.14 (10), p.1218-1225</ispartof><rights>Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4773-c90659e44d9cc29ccd2d27df85abdbc799cacc08ccdabda1c3e21ce7b69b05c93</citedby><cites>FETCH-LOGICAL-c4773-c90659e44d9cc29ccd2d27df85abdbc799cacc08ccdabda1c3e21ce7b69b05c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcbic.201300163$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcbic.201300163$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23780915$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hau, Jean Christophe</creatorcontrib><creatorcontrib>Erdmann, Dirk</creatorcontrib><creatorcontrib>Mesrouze, Yannick</creatorcontrib><creatorcontrib>Furet, Pascal</creatorcontrib><creatorcontrib>Fontana, Patrizia</creatorcontrib><creatorcontrib>Zimmermann, Catherine</creatorcontrib><creatorcontrib>Schmelzle, Tobias</creatorcontrib><creatorcontrib>Hofmann, Francesco</creatorcontrib><creatorcontrib>Chène, Patrick</creatorcontrib><title>The TEAD4-YAP/TAZ Protein-Protein Interaction: Expected Similarities and Unexpected Differences</title><title>Chembiochem : a European journal of chemical biology</title><addtitle>ChemBioChem</addtitle><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.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Binding sites</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Hippo pathway</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Muscle Proteins - chemistry</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle Proteins - metabolism</subject><subject>Mutagenesis, Site-Directed</subject><subject>omega loops</subject><subject>peptides</subject><subject>Peptides - chemistry</subject><subject>Peptides - genetics</subject><subject>Peptides - metabolism</subject><subject>Protein Interaction Domains and Motifs</subject><subject>protein-protein interactions</subject><subject>Protein-Serine-Threonine Kinases - chemistry</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Sequence Homology, Amino Acid</subject><subject>Signal Transduction</subject><subject>TAZ</subject><subject>TEAD</subject><subject>Transcription Factors - chemistry</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>YAP</subject><issn>1439-4227</issn><issn>1439-7633</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1v2zAMxYWhxdpmve44GOjZKSXZVrRbmqRpgGILNqfDdhFkmsbUJXYqOWj639dFPtDbDgQJ8vcegcfYZw59DiCusXDYF8AlAM_kB3bOE6ljlUl5sp8TIdQZuwjhEQB0JvlHdiakGoDm6Tkz-V-K8slwnMS_h_PrfPgnmvumJVfH-x7N6pa8xdY19ddosl0TtlRGP93KLa13raMQ2bqMFjUdbmNXVeSpRgqf2Glll4Eu973HFreTfHQX33-fzkbD-xgTpWSMGrJUU5KUGlF0VYpSqLIapLYoC1Rao0WEQXfoFpajJMGRVJHpAlLUsseudr5r3zxtKLTmsdn4untpuFQiVQAZdFR_R6FvQvBUmbV3K-tfDAfzlqd5y9Mc8-wEX_a2m2JF5RE_BNgBegc8uyW9_MfOjG5mo_fm8U7rQkvbo9b6fyZTUqXm17epecj5eJpP5-aHfAXDnpFV</recordid><startdate>20130708</startdate><enddate>20130708</enddate><creator>Hau, Jean Christophe</creator><creator>Erdmann, Dirk</creator><creator>Mesrouze, Yannick</creator><creator>Furet, Pascal</creator><creator>Fontana, Patrizia</creator><creator>Zimmermann, Catherine</creator><creator>Schmelzle, Tobias</creator><creator>Hofmann, Francesco</creator><creator>Chène, Patrick</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope></search><sort><creationdate>20130708</creationdate><title>The TEAD4-YAP/TAZ Protein-Protein Interaction: Expected Similarities and Unexpected Differences</title><author>Hau, Jean Christophe ; 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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.
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.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>23780915</pmid><doi>10.1002/cbic.201300163</doi><tpages>8</tpages></addata></record> |
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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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