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Nat Struct Mol Biol. 2013 Jun;20(6):740-7. doi: 10.1038/nsmb.2568. Epub 2013 May 5.

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

Author information

1
Genomic Medicine Program, The Methodist Hospital Research Institute, Houston, Texas, USA.

Abstract

IscR from Escherichia coli is an unusual metalloregulator in that both apo and iron sulfur (Fe-S)-IscR regulate transcription and exhibit different DNA binding specificities. Here, we report structural and biochemical studies of IscR suggesting that remodeling of the protein-DNA interface upon Fe-S ligation broadens the DNA binding specificity of IscR from binding the type 2 motif only to both type 1 and type 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 type 2 motifs. These data suggest a unique 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.

PMID:
23644595
PMCID:
PMC3676455
DOI:
10.1038/nsmb.2568
[Indexed for MEDLINE]
Free PMC Article

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