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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...

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Autores principales: Park, Sun Cheol, Kwak, Yun Mi, Song, Wan Seok, Hong, Minsun, Yoon, Sung-il
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
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.
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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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