Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators

Abstract Ferric uptake regulators (Fur) are a family of transcription factors coupling gene regulatory events to metal concentration. Recent evidence has expanded the mechanistic repertoires employed by Fur to activate or repress gene expression in the presence or absence of regulatory metals. Howev...

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Autores principales:	Sabina Sarvan, François Charih, Momen Askoura, James Butcher, Joseph S. Brunzelle, Alain Stintzi, Jean-François Couture
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ff782a99ead4442ae617401d085679a
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spelling	oai:doaj.org-article:1ff782a99ead4442ae617401d085679a2021-12-02T12:32:35ZFunctional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators10.1038/s41598-018-25157-62045-2322https://doaj.org/article/1ff782a99ead4442ae617401d085679a2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25157-6https://doaj.org/toc/2045-2322Abstract Ferric uptake regulators (Fur) are a family of transcription factors coupling gene regulatory events to metal concentration. Recent evidence has expanded the mechanistic repertoires employed by Fur to activate or repress gene expression in the presence or absence of regulatory metals. However, the mechanistic basis underlying this extended repertoire has remained largely unexplored. In this study, we used an extensive set of mutations to demonstrate that Campylobacter jejuni Fur (CjFur) employs the same surface to positively and negatively control gene expression regardless of the presence or absence of metals. Moreover, the crystal structure determination of a CjFur devoid of any regulatory metals shows that subtle reorientation of the transcription factor DNA binding domain negatively impacts DNA binding, gene expression and gut colonization in chickens. Overall, these results highlight the versatility of the CjFur DNA binding domain in mediating all gene regulatory events controlled by the metalloregulator and that the full metalation of CjFur is critical to the Campylobacter jejuni life cycle in vivo.Sabina SarvanFrançois CharihMomen AskouraJames ButcherJoseph S. BrunzelleAlain StintziJean-François CoutureNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sabina Sarvan François Charih Momen Askoura James Butcher Joseph S. Brunzelle Alain Stintzi Jean-François Couture Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators
description	Abstract Ferric uptake regulators (Fur) are a family of transcription factors coupling gene regulatory events to metal concentration. Recent evidence has expanded the mechanistic repertoires employed by Fur to activate or repress gene expression in the presence or absence of regulatory metals. However, the mechanistic basis underlying this extended repertoire has remained largely unexplored. In this study, we used an extensive set of mutations to demonstrate that Campylobacter jejuni Fur (CjFur) employs the same surface to positively and negatively control gene expression regardless of the presence or absence of metals. Moreover, the crystal structure determination of a CjFur devoid of any regulatory metals shows that subtle reorientation of the transcription factor DNA binding domain negatively impacts DNA binding, gene expression and gut colonization in chickens. Overall, these results highlight the versatility of the CjFur DNA binding domain in mediating all gene regulatory events controlled by the metalloregulator and that the full metalation of CjFur is critical to the Campylobacter jejuni life cycle in vivo.
format	article
author	Sabina Sarvan François Charih Momen Askoura James Butcher Joseph S. Brunzelle Alain Stintzi Jean-François Couture
author_facet	Sabina Sarvan François Charih Momen Askoura James Butcher Joseph S. Brunzelle Alain Stintzi Jean-François Couture
author_sort	Sabina Sarvan
title	Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators
title_short	Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators
title_full	Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators
title_fullStr	Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators
title_full_unstemmed	Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators
title_sort	functional insights into the interplay between dna interaction and metal coordination in ferric uptake regulators
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1ff782a99ead4442ae617401d085679a
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Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators

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