4HF0

Crystal Structure of Apo IscR

Summary for 4HF0

• Entry DOI: 10.2210/pdb4hf0/pdb
• Related: 4HF1 4HF2
• Descriptor: HTH-type transcriptional regulator IscR, SULFATE ION (3 entities in total)
• Functional Keywords: whth, protein-dna complex, iron-sulfur cluster, winged helix-turn-helix, transcriptional regulator, redox sensor, dna binding, transcription
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 29957.48

Authors

Rajagopalan, S.R.,Phillips, K.J. (deposition date: 2012-10-04, release date: 2013-05-08, Last modification date: 2024-02-28)

Primary citation

Rajagopalan, S.,Teter, S.J.,Zwart, P.H.,Brennan, R.G.,Phillips, K.J.,Kiley, P.J.
Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity.
Nat.Struct.Mol.Biol., 20:740-747, 2013

PubMed 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.

PubMed: 23644595
DOI: 10.1038/nsmb.2568

Experimental method

X-RAY DIFFRACTION (1.9 Å)