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

Published

Journal Article

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.

Full Text

Cited Authors

  • Rajagopalan, S; Teter, SJ; Zwart, PH; Brennan, RG; Phillips, KJ; Kiley, PJ

Published Date

  • June 2013

Published In

Volume / Issue

  • 20 / 6

Start / End Page

  • 740 - 747

PubMed ID

  • 23644595

Pubmed Central ID

  • 23644595

Electronic International Standard Serial Number (EISSN)

  • 1545-9985

International Standard Serial Number (ISSN)

  • 1545-9993

Digital Object Identifier (DOI)

  • 10.1038/nsmb.2568

Language

  • eng