@article{28523ab3bad94a53854ac119fcccd643,
title = "Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity",
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.",
author = "Senapathy Rajagopalan and Teter, {Sarah J.} and Zwart, {Petrus H.} and Brennan, {Richard G.} and Phillips, {Kevin J.} and Kiley, {Patricia J.}",
note = "Funding Information: at Advanced Light Source (ALS) and at the Northeastern Collaborative Access Team (NE-CAT) beamlines at Advanced Photon Source (APS). BCSB is supported in part by the NIH, the National Institute of General Medical Sciences and the Howard Hughes Medical Institute. The ALS is supported by the Director, Office of Science and the Office of Basic Energy Sciences of the US Department of Energy (DOE) under contract no. DE-AC02-05CH11231. The NE-CAT beamlines are supported by grants from the National Center for Research Resources (5P41RR015301-10) and the National Institute of General Medical Sciences (8 P41 GM103403-10). Use of the APS, operated for the DOE Office of Science by Argonne National Laboratory, was supported by the DOE under contract no. DE-AC02-06CH11357. This work was funded by grants from the US National Institutes of Health (NIH; GM045844 to P.J.K.) and The Methodist Hospital Research Institute to K.J.P.",
year = "2013",
month = jun,
doi = "10.1038/nsmb.2568",
language = "English (US)",
volume = "20",
pages = "740--747",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "6",
}