Summary information and primary citation

PDB-id
4hf1; SNAP-derived features in text and JSON formats; DNAproDB
Class
transcription-DNA
Method
X-ray (2.222 Å)
Summary
Crystal structure of iscr bound to its promoter
Reference
Rajagopalan S, Teter SJ, Zwart PH, Brennan RG, Phillips KJ, Kiley PJ (2013): "Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity." Nat.Struct.Mol.Biol., 20, 740-747. doi: 10.1038/nsmb.2568.
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.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js