Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR

Abstract LmrR is a multidrug binding transcriptional repressor that controls the expression of a major multidrug transporter, LmrCD, in Lactococcus lactis. Promiscuous compound ligations reduce the affinity of LmrR for the lmrCD operator by several fold to release the transcriptional repression; how...

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Autores principales:	Koh Takeuchi, Misaki Imai, Ichio Shimada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/741244899c5d4befabe4f587b26af0b9
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spelling	oai:doaj.org-article:741244899c5d4befabe4f587b26af0b92021-12-02T15:05:12ZDynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR10.1038/s41598-017-00257-x2045-2322https://doaj.org/article/741244899c5d4befabe4f587b26af0b92017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00257-xhttps://doaj.org/toc/2045-2322Abstract LmrR is a multidrug binding transcriptional repressor that controls the expression of a major multidrug transporter, LmrCD, in Lactococcus lactis. Promiscuous compound ligations reduce the affinity of LmrR for the lmrCD operator by several fold to release the transcriptional repression; however, the affinity reduction is orders of magnitude smaller than that of typical transcriptional repressors. Here, we found that the transcriptional regulation of LmrR is achieved through an equilibrium between the operator-bound and non-specific DNA-adsorption states in vivo. The effective dissociation constant of LmrR for the lmrCD operator under the equilibrium is close to the endogenous concentration of LmrR, which allows a substantial reduction of LmrR occupancy upon compound ligations. Therefore, LmrR represents a dynamic type of transcriptional regulation of prokaryotic multidrug resistance systems, where the small affinity reduction induced by compounds is coupled to the functional relocalization of the repressor on the genomic DNA via nonspecific DNA adsorption.Koh TakeuchiMisaki ImaiIchio ShimadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Koh Takeuchi Misaki Imai Ichio Shimada Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR
description	Abstract LmrR is a multidrug binding transcriptional repressor that controls the expression of a major multidrug transporter, LmrCD, in Lactococcus lactis. Promiscuous compound ligations reduce the affinity of LmrR for the lmrCD operator by several fold to release the transcriptional repression; however, the affinity reduction is orders of magnitude smaller than that of typical transcriptional repressors. Here, we found that the transcriptional regulation of LmrR is achieved through an equilibrium between the operator-bound and non-specific DNA-adsorption states in vivo. The effective dissociation constant of LmrR for the lmrCD operator under the equilibrium is close to the endogenous concentration of LmrR, which allows a substantial reduction of LmrR occupancy upon compound ligations. Therefore, LmrR represents a dynamic type of transcriptional regulation of prokaryotic multidrug resistance systems, where the small affinity reduction induced by compounds is coupled to the functional relocalization of the repressor on the genomic DNA via nonspecific DNA adsorption.
format	article
author	Koh Takeuchi Misaki Imai Ichio Shimada
author_facet	Koh Takeuchi Misaki Imai Ichio Shimada
author_sort	Koh Takeuchi
title	Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR
title_short	Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR
title_full	Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR
title_fullStr	Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR
title_full_unstemmed	Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR
title_sort	dynamic equilibrium on dna defines transcriptional regulation of a multidrug binding transcriptional repressor, lmrr
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/741244899c5d4befabe4f587b26af0b9
work_keys_str_mv	AT kohtakeuchi dynamicequilibriumondnadefinestranscriptionalregulationofamultidrugbindingtranscriptionalrepressorlmrr AT misakiimai dynamicequilibriumondnadefinestranscriptionalregulationofamultidrugbindingtranscriptionalrepressorlmrr AT ichioshimada dynamicequilibriumondnadefinestranscriptionalregulationofamultidrugbindingtranscriptionalrepressorlmrr
_version_	1718388896609337344

Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR

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