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Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion
The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783167/ https://www.ncbi.nlm.nih.gov/pubmed/23836939 http://dx.doi.org/10.1093/nar/gkt584 |
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author | Chen, Yongheng Zhang, Xiaojun Dantas Machado, Ana Carolina Ding, Yuan Chen, Zhuchu Qin, Peter Z. Rohs, Remo Chen, Lin |
author_facet | Chen, Yongheng Zhang, Xiaojun Dantas Machado, Ana Carolina Ding, Yuan Chen, Zhuchu Qin, Peter Z. Rohs, Remo Chen, Lin |
author_sort | Chen, Yongheng |
collection | PubMed |
description | The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer. |
format | Online Article Text |
id | pubmed-3783167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-37831672013-09-30 Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion Chen, Yongheng Zhang, Xiaojun Dantas Machado, Ana Carolina Ding, Yuan Chen, Zhuchu Qin, Peter Z. Rohs, Remo Chen, Lin Nucleic Acids Res Structural Biology The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer. Oxford University Press 2013-09 2013-08-02 /pmc/articles/PMC3783167/ /pubmed/23836939 http://dx.doi.org/10.1093/nar/gkt584 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Structural Biology Chen, Yongheng Zhang, Xiaojun Dantas Machado, Ana Carolina Ding, Yuan Chen, Zhuchu Qin, Peter Z. Rohs, Remo Chen, Lin Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion |
title | Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion |
title_full | Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion |
title_fullStr | Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion |
title_full_unstemmed | Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion |
title_short | Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion |
title_sort | structure of p53 binding to the bax response element reveals dna unwinding and compression to accommodate base-pair insertion |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783167/ https://www.ncbi.nlm.nih.gov/pubmed/23836939 http://dx.doi.org/10.1093/nar/gkt584 |
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