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Structural insight on the mechanism of regulation of the MarR family of proteins: high-resolution crystal structure of a transcriptional repressor from Methanobacterium thermoautotrophicum.
J Mol Biol. 2008 Mar 28; 377(3):655-67.JM

Abstract

Transcriptional regulators belonging to the MarR family are characterized by a winged-helix DNA binding domain. These transcriptional regulators regulate the efflux and influx of phenolic agents in bacteria and archaea. In Escherichia coli, MarR regulates the multiple antibiotic resistance operon and its inactivation produces a multiple antibiotic resistance phenotype. In some organisms, active efflux of drug compounds will produce a drug resistance phenotype, whereas in other organisms, active influx of chlorinated hydrocarbons results in their rapid degradation. Although proteins in the MarR family are regulators of important biological processes, their mechanism of action is not well understood and structural information about how phenolic agents regulate the activity of these proteins is lacking. This article presents the three-dimensional structure of a protein of the MarR family, MTH313, in its apo form and in complex with salicylate, a known inactivator. A comparison of these two structures indicates that the mechanism of regulation involves a large conformational change in the DNA binding lobe. Electrophoretic mobility shift assay and biophysical analyses further suggest that salicylate inactivates MTH313 and prevents it from binding to its promoter region.

Authors+Show Affiliations

Department of Biology, York University, 4700 Keele Street, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18272181

Citation

Saridakis, Vivian, et al. "Structural Insight On the Mechanism of Regulation of the MarR Family of Proteins: High-resolution Crystal Structure of a Transcriptional Repressor From Methanobacterium Thermoautotrophicum." Journal of Molecular Biology, vol. 377, no. 3, 2008, pp. 655-67.
Saridakis V, Shahinas D, Xu X, et al. Structural insight on the mechanism of regulation of the MarR family of proteins: high-resolution crystal structure of a transcriptional repressor from Methanobacterium thermoautotrophicum. J Mol Biol. 2008;377(3):655-67.
Saridakis, V., Shahinas, D., Xu, X., & Christendat, D. (2008). Structural insight on the mechanism of regulation of the MarR family of proteins: high-resolution crystal structure of a transcriptional repressor from Methanobacterium thermoautotrophicum. Journal of Molecular Biology, 377(3), 655-67. https://doi.org/10.1016/j.jmb.2008.01.001
Saridakis V, et al. Structural Insight On the Mechanism of Regulation of the MarR Family of Proteins: High-resolution Crystal Structure of a Transcriptional Repressor From Methanobacterium Thermoautotrophicum. J Mol Biol. 2008 Mar 28;377(3):655-67. PubMed PMID: 18272181.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural insight on the mechanism of regulation of the MarR family of proteins: high-resolution crystal structure of a transcriptional repressor from Methanobacterium thermoautotrophicum. AU - Saridakis,Vivian, AU - Shahinas,Dea, AU - Xu,Xiaohui, AU - Christendat,Dinesh, Y1 - 2008/01/11/ PY - 2007/10/24/received PY - 2007/12/20/revised PY - 2008/01/02/accepted PY - 2008/2/15/pubmed PY - 2008/5/28/medline PY - 2008/2/15/entrez SP - 655 EP - 67 JF - Journal of molecular biology JO - J Mol Biol VL - 377 IS - 3 N2 - Transcriptional regulators belonging to the MarR family are characterized by a winged-helix DNA binding domain. These transcriptional regulators regulate the efflux and influx of phenolic agents in bacteria and archaea. In Escherichia coli, MarR regulates the multiple antibiotic resistance operon and its inactivation produces a multiple antibiotic resistance phenotype. In some organisms, active efflux of drug compounds will produce a drug resistance phenotype, whereas in other organisms, active influx of chlorinated hydrocarbons results in their rapid degradation. Although proteins in the MarR family are regulators of important biological processes, their mechanism of action is not well understood and structural information about how phenolic agents regulate the activity of these proteins is lacking. This article presents the three-dimensional structure of a protein of the MarR family, MTH313, in its apo form and in complex with salicylate, a known inactivator. A comparison of these two structures indicates that the mechanism of regulation involves a large conformational change in the DNA binding lobe. Electrophoretic mobility shift assay and biophysical analyses further suggest that salicylate inactivates MTH313 and prevents it from binding to its promoter region. SN - 1089-8638 UR - https://www.unboundmedicine.com/medline/citation/18272181/Structural_insight_on_the_mechanism_of_regulation_of_the_MarR_family_of_proteins:_high_resolution_crystal_structure_of_a_transcriptional_repressor_from_Methanobacterium_thermoautotrophicum_ DB - PRIME DP - Unbound Medicine ER -