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The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism.

Publication ,  Journal Article
Draughn, GL; Milton, ME; Feldmann, EA; Bobay, BG; Roth, BM; Olson, AL; Thompson, RJ; Actis, LA; Davies, C; Cavanagh, J
Published in: J Mol Biol
March 16, 2018

The rise of drug-resistant bacterial infections coupled with decreasing antibiotic efficacy poses a significant challenge to global health care. Acinetobacter baumannii is an insidious, emerging bacterial pathogen responsible for severe nosocomial infections aided by its ability to form biofilms. The response regulator BfmR, from the BfmR/S two-component system, is the master regulator of biofilm initiation in A. baumannii and is a tractable therapeutic target. Here we present the structure of A. baumannii BfmR using a hybrid approach combining X-ray crystallography, nuclear magnetic resonance spectroscopy, chemical crosslinking mass spectrometry, and molecular modeling. We also show that BfmR binds the previously proposed bfmRS promoter sequence with moderate affinity. While BfmR shares many traits with other OmpR/PhoB family response regulators, some unusual properties were observed. Most importantly, we observe that when phosphorylated, BfmR binds this promoter sequence with a lower affinity than when not phosphorylated. All other OmpR/PhoB family members studied to date show an increase in DNA-binding affinity upon phosphorylation. Understanding the structural and biochemical mechanisms of BfmR will aid in the development of new antimicrobial therapies.

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Published In

J Mol Biol

DOI

EISSN

1089-8638

Publication Date

March 16, 2018

Volume

430

Issue

6

Start / End Page

806 / 821

Location

Netherlands

Related Subject Headings

  • Protein Conformation
  • Promoter Regions, Genetic
  • Phosphorylation
  • Models, Molecular
  • Gene Expression Regulation, Bacterial
  • DNA-Binding Proteins
  • Crystallography, X-Ray
  • Cloning, Molecular
  • Biofilms
  • Biochemistry & Molecular Biology
 

Citation

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Draughn, G. L., Milton, M. E., Feldmann, E. A., Bobay, B. G., Roth, B. M., Olson, A. L., … Cavanagh, J. (2018). The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism. J Mol Biol, 430(6), 806–821. https://doi.org/10.1016/j.jmb.2018.02.002
Draughn, G Logan, Morgan E. Milton, Erik A. Feldmann, Benjamin G. Bobay, Braden M. Roth, Andrew L. Olson, Richele J. Thompson, Luis A. Actis, Christopher Davies, and John Cavanagh. “The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism.J Mol Biol 430, no. 6 (March 16, 2018): 806–21. https://doi.org/10.1016/j.jmb.2018.02.002.
Draughn GL, Milton ME, Feldmann EA, Bobay BG, Roth BM, Olson AL, et al. The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism. J Mol Biol. 2018 Mar 16;430(6):806–21.
Draughn, G. Logan, et al. “The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism.J Mol Biol, vol. 430, no. 6, Mar. 2018, pp. 806–21. Pubmed, doi:10.1016/j.jmb.2018.02.002.
Draughn GL, Milton ME, Feldmann EA, Bobay BG, Roth BM, Olson AL, Thompson RJ, Actis LA, Davies C, Cavanagh J. The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism. J Mol Biol. 2018 Mar 16;430(6):806–821.
Journal cover image

Published In

J Mol Biol

DOI

EISSN

1089-8638

Publication Date

March 16, 2018

Volume

430

Issue

6

Start / End Page

806 / 821

Location

Netherlands

Related Subject Headings

  • Protein Conformation
  • Promoter Regions, Genetic
  • Phosphorylation
  • Models, Molecular
  • Gene Expression Regulation, Bacterial
  • DNA-Binding Proteins
  • Crystallography, X-Ray
  • Cloning, Molecular
  • Biofilms
  • Biochemistry & Molecular Biology