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Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD
Yes-associated protein (YAP) is a partly intrinsically disordered protein (IDP) that plays a major role as the downstream element of the Hippo pathway. Although the structures of the complex between TEA domain transcription factors (TEADs) and the TEAD-binding domain of YAP are already well characte...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976148/ https://www.ncbi.nlm.nih.gov/pubmed/35378854 http://dx.doi.org/10.1016/j.isci.2022.104099 |
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author | Feichtinger, Michael Beier, Andreas Migotti, Mario Schmid, Matthias Bokhovchuk, Fedir Chène, Patrick Konrat, Robert |
author_facet | Feichtinger, Michael Beier, Andreas Migotti, Mario Schmid, Matthias Bokhovchuk, Fedir Chène, Patrick Konrat, Robert |
author_sort | Feichtinger, Michael |
collection | PubMed |
description | Yes-associated protein (YAP) is a partly intrinsically disordered protein (IDP) that plays a major role as the downstream element of the Hippo pathway. Although the structures of the complex between TEA domain transcription factors (TEADs) and the TEAD-binding domain of YAP are already well characterized, its apo state and the binding mechanism with TEADs are still not clearly defined. Here we characterize via a combination of different NMR approaches with site-directed mutagenesis and affinity measurements the intrinsically disordered solution state of apo YAP. Our results provide evidence that the apo state of YAP adopts several compact conformations that may facilitate the formation of the YAP:TEAD complex. The interplay between local secondary structure element preformation and long-range co-stabilization of these structured elements precedes the encounter complex formation with TEAD and we, therefore, propose that TEAD binding proceeds largely via conformational selection of the preformed compact substates displaying at least nanosecond lifetimes. |
format | Online Article Text |
id | pubmed-8976148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-89761482022-04-03 Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD Feichtinger, Michael Beier, Andreas Migotti, Mario Schmid, Matthias Bokhovchuk, Fedir Chène, Patrick Konrat, Robert iScience Article Yes-associated protein (YAP) is a partly intrinsically disordered protein (IDP) that plays a major role as the downstream element of the Hippo pathway. Although the structures of the complex between TEA domain transcription factors (TEADs) and the TEAD-binding domain of YAP are already well characterized, its apo state and the binding mechanism with TEADs are still not clearly defined. Here we characterize via a combination of different NMR approaches with site-directed mutagenesis and affinity measurements the intrinsically disordered solution state of apo YAP. Our results provide evidence that the apo state of YAP adopts several compact conformations that may facilitate the formation of the YAP:TEAD complex. The interplay between local secondary structure element preformation and long-range co-stabilization of these structured elements precedes the encounter complex formation with TEAD and we, therefore, propose that TEAD binding proceeds largely via conformational selection of the preformed compact substates displaying at least nanosecond lifetimes. Elsevier 2022-03-17 /pmc/articles/PMC8976148/ /pubmed/35378854 http://dx.doi.org/10.1016/j.isci.2022.104099 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Feichtinger, Michael Beier, Andreas Migotti, Mario Schmid, Matthias Bokhovchuk, Fedir Chène, Patrick Konrat, Robert Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD |
title | Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD |
title_full | Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD |
title_fullStr | Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD |
title_full_unstemmed | Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD |
title_short | Long-range structural preformation in yes-associated protein precedes encounter complex formation with TEAD |
title_sort | long-range structural preformation in yes-associated protein precedes encounter complex formation with tead |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976148/ https://www.ncbi.nlm.nih.gov/pubmed/35378854 http://dx.doi.org/10.1016/j.isci.2022.104099 |
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