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Molecular mechanisms of ligand-mediated attenuation of DNA binding by MarR family transcriptional regulators.
J Mol Cell Biol. 2010 Oct; 2(5):243-54.JM

Abstract

Bacteria and archaea encode members of the large multiple antibiotic resistance regulator (MarR) family of transcriptional regulators. Generally, MarR homologs regulate activity of genes involved in antibiotic resistance, stress responses, virulence or catabolism of aromatic compounds. They constitute a diverse group of transcriptional regulators that includes both repressors and activators, and the conventional mode of regulation entails a genetic locus in which the MarR homolog and a gene under its regulation are encoded divergently; binding of the MarR homolog to the intergenic region typically represses transcription of both genes, while binding of a specific ligand to the transcription factor results in attenuated DNA binding and hence activated gene expression. For many homologs, the natural ligand is unknown. Crystal structures reveal a common architecture with a characteristic winged helix domain for DNA binding, and recent structural information of homologs solved both in the absence and presence of their respective ligands, as well as biochemical data, is finally converging to illuminate the mechanisms by which ligand-binding causes attenuated DNA binding. As MarR homologs regulate pathways that are critical to bacterial physiology, including virulence, a molecular understanding of mechanisms by which ligands affect a regulation of gene activity is essential. Specifying the position of ligand-binding pockets further has the potential to aid in identifying the ligands for MarR homologs for which the ligand remains unknown.

Authors+Show Affiliations

Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

20716550

Citation

Perera, Inoka C., and Anne Grove. "Molecular Mechanisms of Ligand-mediated Attenuation of DNA Binding By MarR Family Transcriptional Regulators." Journal of Molecular Cell Biology, vol. 2, no. 5, 2010, pp. 243-54.
Perera IC, Grove A. Molecular mechanisms of ligand-mediated attenuation of DNA binding by MarR family transcriptional regulators. J Mol Cell Biol. 2010;2(5):243-54.
Perera, I. C., & Grove, A. (2010). Molecular mechanisms of ligand-mediated attenuation of DNA binding by MarR family transcriptional regulators. Journal of Molecular Cell Biology, 2(5), 243-54. https://doi.org/10.1093/jmcb/mjq021
Perera IC, Grove A. Molecular Mechanisms of Ligand-mediated Attenuation of DNA Binding By MarR Family Transcriptional Regulators. J Mol Cell Biol. 2010;2(5):243-54. PubMed PMID: 20716550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular mechanisms of ligand-mediated attenuation of DNA binding by MarR family transcriptional regulators. AU - Perera,Inoka C, AU - Grove,Anne, Y1 - 2010/08/17/ PY - 2010/8/19/entrez PY - 2010/8/19/pubmed PY - 2011/1/6/medline SP - 243 EP - 54 JF - Journal of molecular cell biology JO - J Mol Cell Biol VL - 2 IS - 5 N2 - Bacteria and archaea encode members of the large multiple antibiotic resistance regulator (MarR) family of transcriptional regulators. Generally, MarR homologs regulate activity of genes involved in antibiotic resistance, stress responses, virulence or catabolism of aromatic compounds. They constitute a diverse group of transcriptional regulators that includes both repressors and activators, and the conventional mode of regulation entails a genetic locus in which the MarR homolog and a gene under its regulation are encoded divergently; binding of the MarR homolog to the intergenic region typically represses transcription of both genes, while binding of a specific ligand to the transcription factor results in attenuated DNA binding and hence activated gene expression. For many homologs, the natural ligand is unknown. Crystal structures reveal a common architecture with a characteristic winged helix domain for DNA binding, and recent structural information of homologs solved both in the absence and presence of their respective ligands, as well as biochemical data, is finally converging to illuminate the mechanisms by which ligand-binding causes attenuated DNA binding. As MarR homologs regulate pathways that are critical to bacterial physiology, including virulence, a molecular understanding of mechanisms by which ligands affect a regulation of gene activity is essential. Specifying the position of ligand-binding pockets further has the potential to aid in identifying the ligands for MarR homologs for which the ligand remains unknown. SN - 1759-4685 UR - https://www.unboundmedicine.com/medline/citation/20716550/Molecular_mechanisms_of_ligand_mediated_attenuation_of_DNA_binding_by_MarR_family_transcriptional_regulators_ L2 - https://academic.oup.com/jmcb/article-lookup/doi/10.1093/jmcb/mjq021 DB - PRIME DP - Unbound Medicine ER -