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Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein
Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding upon binding’ process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766501/ https://www.ncbi.nlm.nih.gov/pubmed/26912067 http://dx.doi.org/10.1038/srep21994 |
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author | Toto, Angelo Camilloni, Carlo Giri, Rajanish Brunori, Maurizio Vendruscolo, Michele Gianni, Stefano |
author_facet | Toto, Angelo Camilloni, Carlo Giri, Rajanish Brunori, Maurizio Vendruscolo, Michele Gianni, Stefano |
author_sort | Toto, Angelo |
collection | PubMed |
description | Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding upon binding’ process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb (c-Myb) upon binding its partner KIX. By determining the structure of the folding transition state for the binding of wild-type and three mutational variants of KIX, we found a remarkable plasticity of the folding pathway of c-Myb. To explain this phenomenon, we show that the folding of c-Myb is templated by the structure of KIX. This adaptive folding behaviour, which occurs by heterogeneous nucleation, differs from the robust homogeneous nucleation typically observed for globular proteins. We suggest that this templated folding mechanism may enable intrinsically disordered proteins to achieve specific and reliable binding with multiple partners while avoiding aberrant interactions. |
format | Online Article Text |
id | pubmed-4766501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47665012016-03-02 Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein Toto, Angelo Camilloni, Carlo Giri, Rajanish Brunori, Maurizio Vendruscolo, Michele Gianni, Stefano Sci Rep Article Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding upon binding’ process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb (c-Myb) upon binding its partner KIX. By determining the structure of the folding transition state for the binding of wild-type and three mutational variants of KIX, we found a remarkable plasticity of the folding pathway of c-Myb. To explain this phenomenon, we show that the folding of c-Myb is templated by the structure of KIX. This adaptive folding behaviour, which occurs by heterogeneous nucleation, differs from the robust homogeneous nucleation typically observed for globular proteins. We suggest that this templated folding mechanism may enable intrinsically disordered proteins to achieve specific and reliable binding with multiple partners while avoiding aberrant interactions. Nature Publishing Group 2016-02-25 /pmc/articles/PMC4766501/ /pubmed/26912067 http://dx.doi.org/10.1038/srep21994 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Toto, Angelo Camilloni, Carlo Giri, Rajanish Brunori, Maurizio Vendruscolo, Michele Gianni, Stefano Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein |
title | Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein |
title_full | Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein |
title_fullStr | Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein |
title_full_unstemmed | Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein |
title_short | Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein |
title_sort | molecular recognition by templated folding of an intrinsically disordered protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766501/ https://www.ncbi.nlm.nih.gov/pubmed/26912067 http://dx.doi.org/10.1038/srep21994 |
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