Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)

Antibiotic production and resistance pathways in Streptomyces are dictated by the interplay of transcriptional regulatory proteins that trigger downstream responses via binding to small diffusible molecules. To decipher the mode of DNA binding and the associated allosteric mechanism in the sub-class...

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Main Authors:	Bhukya, Hussain, Bhujbalrao, Ruchika, Bitra, Aruna, Anand, Ruchi
Format:	Online
Language:	English
Published:	Oxford University Press 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150764/

id	pubmed-4150764
recordtype	oai_dc
spelling	pubmed-41507642014-12-01 Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2) Bhukya, Hussain Bhujbalrao, Ruchika Bitra, Aruna Anand, Ruchi Structural Biology Antibiotic production and resistance pathways in Streptomyces are dictated by the interplay of transcriptional regulatory proteins that trigger downstream responses via binding to small diffusible molecules. To decipher the mode of DNA binding and the associated allosteric mechanism in the sub-class of transcription factors that are induced by γ-butyrolactones, we present the crystal structure of CprB in complex with the consensus DNA element to a resolution of 3.25 Å. Binding of the DNA results in the restructuring of the dimeric interface of CprB, inducing a pendulum-like motion of the helix-turn-helix motif that inserts into the major groove. The crystal structure revealed that, CprB is bound to DNA as a dimer of dimers with the mode of binding being analogous to the broad spectrum multidrug transporter protein QacR from the antibiotic resistant strain Staphylococcus aureus. It was demonstrated that the CprB displays a cooperative mode of DNA binding, following a clamp and click model. Experiments performed on a subset of DNA sequences from Streptomyces coelicolor A3(2) suggest that CprB is most likely a pleiotropic regulator. Apart from serving as an autoregulator, it is potentially a part of a network of proteins that modulates the γ-butyrolactone synthesis and antibiotic regulation pathways in S. coelicolor A3(2). Oxford University Press 2014-09-02 2014-08-04 /pmc/articles/PMC4150764/ /pubmed/25092919 http://dx.doi.org/10.1093/nar/gku587 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Bhukya, Hussain Bhujbalrao, Ruchika Bitra, Aruna Anand, Ruchi
spellingShingle	Bhukya, Hussain Bhujbalrao, Ruchika Bitra, Aruna Anand, Ruchi Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)
author_facet	Bhukya, Hussain Bhujbalrao, Ruchika Bitra, Aruna Anand, Ruchi
author_sort	Bhukya, Hussain
title	Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)
title_short	Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)
title_full	Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)
title_fullStr	Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)
title_full_unstemmed	Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)
title_sort	structural and functional basis of transcriptional regulation by tetr family protein cprb from s. coelicolor a3(2)
description	Antibiotic production and resistance pathways in Streptomyces are dictated by the interplay of transcriptional regulatory proteins that trigger downstream responses via binding to small diffusible molecules. To decipher the mode of DNA binding and the associated allosteric mechanism in the sub-class of transcription factors that are induced by γ-butyrolactones, we present the crystal structure of CprB in complex with the consensus DNA element to a resolution of 3.25 Å. Binding of the DNA results in the restructuring of the dimeric interface of CprB, inducing a pendulum-like motion of the helix-turn-helix motif that inserts into the major groove. The crystal structure revealed that, CprB is bound to DNA as a dimer of dimers with the mode of binding being analogous to the broad spectrum multidrug transporter protein QacR from the antibiotic resistant strain Staphylococcus aureus. It was demonstrated that the CprB displays a cooperative mode of DNA binding, following a clamp and click model. Experiments performed on a subset of DNA sequences from Streptomyces coelicolor A3(2) suggest that CprB is most likely a pleiotropic regulator. Apart from serving as an autoregulator, it is potentially a part of a network of proteins that modulates the γ-butyrolactone synthesis and antibiotic regulation pathways in S. coelicolor A3(2).
publisher	Oxford University Press
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150764/
_version_	1613129849970360320

Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)

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