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Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR
The PadR family is a large group of transcriptional regulators that function as environmental sensors. PadR negatively controls the expression of phenolic acid decarboxylase, which detoxifies harmful phenolic acids. To identify the mechanism by which PadR regulates phenolic acid-mediated gene expres...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728393/ https://www.ncbi.nlm.nih.gov/pubmed/29136175 http://dx.doi.org/10.1093/nar/gkx1055 |
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author | Park, Sun Cheol Kwak, Yun Mi Song, Wan Seok Hong, Minsun Yoon, Sung-il |
author_facet | Park, Sun Cheol Kwak, Yun Mi Song, Wan Seok Hong, Minsun Yoon, Sung-il |
author_sort | Park, Sun Cheol |
collection | PubMed |
description | The PadR family is a large group of transcriptional regulators that function as environmental sensors. PadR negatively controls the expression of phenolic acid decarboxylase, which detoxifies harmful phenolic acids. To identify the mechanism by which PadR regulates phenolic acid-mediated gene expression, we performed structural and mutational studies of effector and operator recognition by Bacillus subtilis PadR. PadR contains an N-terminal winged helix-turn-helix (wHTH) domain (NTD) and a C-terminal homodimerization domain (CTD) and dimerizes into a dolmen shape. The PadR dimer interacts with the palindromic sequence of the operator DNA using the NTD. Two tyrosine residues and a positively charged residue in the NTD provide major DNA-binding energy and are highly conserved in the PadR family, suggesting that these three residues represent the canonical DNA-binding motif of the PadR family. PadR directly binds a phenolic acid effector molecule using a unique interdomain pocket created between the NTD and the CTD. Although the effector-binding site of PadR is positionally segregated from the DNA-binding site, effector binding to the interdomain pocket causes PadR to be rearranged into a DNA binding-incompatible conformer through an allosteric interdomain-reorganization mechanism. |
format | Online Article Text |
id | pubmed-5728393 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57283932017-12-18 Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR Park, Sun Cheol Kwak, Yun Mi Song, Wan Seok Hong, Minsun Yoon, Sung-il Nucleic Acids Res Structural Biology The PadR family is a large group of transcriptional regulators that function as environmental sensors. PadR negatively controls the expression of phenolic acid decarboxylase, which detoxifies harmful phenolic acids. To identify the mechanism by which PadR regulates phenolic acid-mediated gene expression, we performed structural and mutational studies of effector and operator recognition by Bacillus subtilis PadR. PadR contains an N-terminal winged helix-turn-helix (wHTH) domain (NTD) and a C-terminal homodimerization domain (CTD) and dimerizes into a dolmen shape. The PadR dimer interacts with the palindromic sequence of the operator DNA using the NTD. Two tyrosine residues and a positively charged residue in the NTD provide major DNA-binding energy and are highly conserved in the PadR family, suggesting that these three residues represent the canonical DNA-binding motif of the PadR family. PadR directly binds a phenolic acid effector molecule using a unique interdomain pocket created between the NTD and the CTD. Although the effector-binding site of PadR is positionally segregated from the DNA-binding site, effector binding to the interdomain pocket causes PadR to be rearranged into a DNA binding-incompatible conformer through an allosteric interdomain-reorganization mechanism. Oxford University Press 2017-12-15 2017-11-09 /pmc/articles/PMC5728393/ /pubmed/29136175 http://dx.doi.org/10.1093/nar/gkx1055 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), 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 Park, Sun Cheol Kwak, Yun Mi Song, Wan Seok Hong, Minsun Yoon, Sung-il Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR |
title | Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR |
title_full | Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR |
title_fullStr | Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR |
title_full_unstemmed | Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR |
title_short | Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR |
title_sort | structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator padr |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728393/ https://www.ncbi.nlm.nih.gov/pubmed/29136175 http://dx.doi.org/10.1093/nar/gkx1055 |
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