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Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity

IscR from Escherichia coli is an unusual metalloregulator in that it globally regulates transcription by recognizing two different DNA motifs in a Fe-S dependent manner. Here, we report structural and biochemical studies of IscR, which suggest remodeling of the protein-DNA interface upon Fe-S ligati...

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Autores principales: Rajagopalan, Senapathy, Teter, Sarah J., Zwart, Petrus H., Brennan, Richard G., Phillips, Kevin J., Kiley, Patricia J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676455/
https://www.ncbi.nlm.nih.gov/pubmed/23644595
http://dx.doi.org/10.1038/nsmb.2568
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author Rajagopalan, Senapathy
Teter, Sarah J.
Zwart, Petrus H.
Brennan, Richard G.
Phillips, Kevin J.
Kiley, Patricia J.
author_facet Rajagopalan, Senapathy
Teter, Sarah J.
Zwart, Petrus H.
Brennan, Richard G.
Phillips, Kevin J.
Kiley, Patricia J.
author_sort Rajagopalan, Senapathy
collection PubMed
description IscR from Escherichia coli is an unusual metalloregulator in that it globally regulates transcription by recognizing two different DNA motifs in a Fe-S dependent manner. Here, we report structural and biochemical studies of IscR, which suggest remodeling of the protein-DNA interface upon Fe-S ligation broadens the DNA binding specificity from binding a type 2 motif to both type 1 and 2 motifs. Analysis of an apo-IscR variant with relaxed target-site discrimination identified a key residue in wild-type apo-IscR that we propose makes unfavorable interactions with a type 1 motif. Upon Fe-S binding, these interactions are apparently removed, thereby allowing holo-IscR to bind both type 1 and 2 motifs. These data suggest a novel mechanism of ligand-mediated DNA site recognition, whereby metallocluster ligation relocates a protein specificity determinant to expand DNA target site selection, allowing a broader transcriptomic response by holo-IscR.
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spelling pubmed-36764552013-12-01 Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity Rajagopalan, Senapathy Teter, Sarah J. Zwart, Petrus H. Brennan, Richard G. Phillips, Kevin J. Kiley, Patricia J. Nat Struct Mol Biol Article IscR from Escherichia coli is an unusual metalloregulator in that it globally regulates transcription by recognizing two different DNA motifs in a Fe-S dependent manner. Here, we report structural and biochemical studies of IscR, which suggest remodeling of the protein-DNA interface upon Fe-S ligation broadens the DNA binding specificity from binding a type 2 motif to both type 1 and 2 motifs. Analysis of an apo-IscR variant with relaxed target-site discrimination identified a key residue in wild-type apo-IscR that we propose makes unfavorable interactions with a type 1 motif. Upon Fe-S binding, these interactions are apparently removed, thereby allowing holo-IscR to bind both type 1 and 2 motifs. These data suggest a novel mechanism of ligand-mediated DNA site recognition, whereby metallocluster ligation relocates a protein specificity determinant to expand DNA target site selection, allowing a broader transcriptomic response by holo-IscR. 2013-05-05 2013-06 /pmc/articles/PMC3676455/ /pubmed/23644595 http://dx.doi.org/10.1038/nsmb.2568 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Rajagopalan, Senapathy
Teter, Sarah J.
Zwart, Petrus H.
Brennan, Richard G.
Phillips, Kevin J.
Kiley, Patricia J.
Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
title Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
title_full Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
title_fullStr Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
title_full_unstemmed Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
title_short Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
title_sort studies of iscr reveal a unique mechanism for metal-dependent regulation of dna binding specificity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676455/
https://www.ncbi.nlm.nih.gov/pubmed/23644595
http://dx.doi.org/10.1038/nsmb.2568
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