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Solution structure and binding specificity of the p63 DNA binding domain
p63 is a close homologue of p53 and, together with p73, is grouped into the p53 family of transcription factors. p63 is known to be involved in the induction of controlled apoptosis important for differentiation processes, germ line integrity and development. Despite its high homology to p53, especi...
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/PMC4880913/ https://www.ncbi.nlm.nih.gov/pubmed/27225672 http://dx.doi.org/10.1038/srep26707 |
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author | Enthart, Andreas Klein, Christian Dehner, Alexander Coles, Murray Gemmecker, Gerd Kessler, Horst Hagn, Franz |
author_facet | Enthart, Andreas Klein, Christian Dehner, Alexander Coles, Murray Gemmecker, Gerd Kessler, Horst Hagn, Franz |
author_sort | Enthart, Andreas |
collection | PubMed |
description | p63 is a close homologue of p53 and, together with p73, is grouped into the p53 family of transcription factors. p63 is known to be involved in the induction of controlled apoptosis important for differentiation processes, germ line integrity and development. Despite its high homology to p53, especially within the DNA binding domain (DBD), p63-DBD does not show cooperative DNA binding properties and is significantly more stable against thermal and chemical denaturation. Here, we determined the solution structure of p63-DBD and show that it is markedly less dynamic than p53-DBD. In addition, we also investigate the effect of a double salt bridge present in p53-DBD, but not in p63-DBD on the cooperative binding behavior and specificity to various DNA sites. Restoration of the salt bridges in p63-DBD by mutagenesis leads to enhanced binding affinity to p53-specific, but not p63-specific response elements. Furthermore, we show that p63-DBD is capable of binding to anti-apoptotic BclxL via its DNA binding interface, a feature that has only been shown for p53 so far. These data suggest that all p53 family members - despite alterations in the specificity and binding affinity - are capable of activating pro-apoptotic pathways in a tissue specific manner. |
format | Online Article Text |
id | pubmed-4880913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48809132016-06-07 Solution structure and binding specificity of the p63 DNA binding domain Enthart, Andreas Klein, Christian Dehner, Alexander Coles, Murray Gemmecker, Gerd Kessler, Horst Hagn, Franz Sci Rep Article p63 is a close homologue of p53 and, together with p73, is grouped into the p53 family of transcription factors. p63 is known to be involved in the induction of controlled apoptosis important for differentiation processes, germ line integrity and development. Despite its high homology to p53, especially within the DNA binding domain (DBD), p63-DBD does not show cooperative DNA binding properties and is significantly more stable against thermal and chemical denaturation. Here, we determined the solution structure of p63-DBD and show that it is markedly less dynamic than p53-DBD. In addition, we also investigate the effect of a double salt bridge present in p53-DBD, but not in p63-DBD on the cooperative binding behavior and specificity to various DNA sites. Restoration of the salt bridges in p63-DBD by mutagenesis leads to enhanced binding affinity to p53-specific, but not p63-specific response elements. Furthermore, we show that p63-DBD is capable of binding to anti-apoptotic BclxL via its DNA binding interface, a feature that has only been shown for p53 so far. These data suggest that all p53 family members - despite alterations in the specificity and binding affinity - are capable of activating pro-apoptotic pathways in a tissue specific manner. Nature Publishing Group 2016-05-26 /pmc/articles/PMC4880913/ /pubmed/27225672 http://dx.doi.org/10.1038/srep26707 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 Enthart, Andreas Klein, Christian Dehner, Alexander Coles, Murray Gemmecker, Gerd Kessler, Horst Hagn, Franz Solution structure and binding specificity of the p63 DNA binding domain |
title | Solution structure and binding specificity of the p63 DNA binding domain |
title_full | Solution structure and binding specificity of the p63 DNA binding domain |
title_fullStr | Solution structure and binding specificity of the p63 DNA binding domain |
title_full_unstemmed | Solution structure and binding specificity of the p63 DNA binding domain |
title_short | Solution structure and binding specificity of the p63 DNA binding domain |
title_sort | solution structure and binding specificity of the p63 dna binding domain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880913/ https://www.ncbi.nlm.nih.gov/pubmed/27225672 http://dx.doi.org/10.1038/srep26707 |
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