| Structural highlights
Function
[ISCR_ECOLI] Regulates the transcription of several operons and genes involved in the biogenesis of Fe-S clusters and Fe-S-containing proteins. Transcriptional repressor of the iscRSUA operon, which is involved in the assembly of Fe-S clusters into Fe-S proteins. In its apoform, under conditions of oxidative stress or iron deprivation, it activates the suf operon, which is a second operon involved in the assembly of Fe-S clusters. Represses its own transcription as well as that of toxin rnlA.[1] [2] [3]
Publication Abstract from PubMed
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.
Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity.,Rajagopalan S, Teter SJ, Zwart PH, Brennan RG, Phillips KJ, Kiley PJ Nat Struct Mol Biol. 2013 Jun;20(6):740-7. doi: 10.1038/nsmb.2568. Epub 2013 May , 5. PMID:23644595[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schwartz CJ, Giel JL, Patschkowski T, Luther C, Ruzicka FJ, Beinert H, Kiley PJ. IscR, an Fe-S cluster-containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14895-900. Epub 2001 Dec 11. PMID:11742080 doi:10.1073/pnas.251550898
- ↑ Yeo WS, Lee JH, Lee KC, Roe JH. IscR acts as an activator in response to oxidative stress for the suf operon encoding Fe-S assembly proteins. Mol Microbiol. 2006 Jul;61(1):206-18. PMID:16824106 doi:10.1111/j.1365-2958.2006.05220.x
- ↑ Otsuka Y, Miki K, Koga M, Katayama N, Morimoto W, Takahashi Y, Yonesaki T. IscR regulates RNase LS activity by repressing rnlA transcription. Genetics. 2010 Jul;185(3):823-30. doi: 10.1534/genetics.110.114462. Epub 2010 Apr, 26. PMID:20421606 doi:10.1534/genetics.110.114462
- ↑ Rajagopalan S, Teter SJ, Zwart PH, Brennan RG, Phillips KJ, Kiley PJ. Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity. Nat Struct Mol Biol. 2013 Jun;20(6):740-7. doi: 10.1038/nsmb.2568. Epub 2013 May , 5. PMID:23644595 doi:10.1038/nsmb.2568
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