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The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development.

Publication ,  Journal Article
Schumacher, MA; den Hengst, CD; Bush, MJ; Le, TBK; Tran, NT; Chandra, G; Zeng, W; Travis, B; Brennan, RG; Buttner, MJ
Published in: Nat Commun
March 19, 2018

Streptomycetes are notable for their complex life cycle and production of most clinically important antibiotics. A key factor that controls entry into development and the onset of antibiotic production is the 68-residue protein, BldC. BldC is a putative DNA-binding protein related to MerR regulators, but lacks coiled-coil dimerization and effector-binding domains characteristic of classical MerR proteins. Hence, the molecular function of the protein has been unclear. Here we show that BldC is indeed a DNA-binding protein and controls a regulon that includes other key developmental regulators. Intriguingly, BldC DNA-binding sites vary significantly in length. Our BldC-DNA structures explain this DNA-binding capability by revealing that BldC utilizes a DNA-binding mode distinct from MerR and other known regulators, involving asymmetric head-to-tail oligomerization on DNA direct repeats that results in dramatic DNA distortion. Notably, BldC-like proteins radiate throughout eubacteria, establishing BldC as the founding member of a new structural family of regulators.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

March 19, 2018

Volume

9

Issue

1

Start / End Page

1139

Location

England

Related Subject Headings

  • Streptomyces coelicolor
  • Static Electricity
  • Repressor Proteins
  • Repetitive Sequences, Nucleic Acid
  • Regulon
  • Protein Structure, Quaternary
  • Promoter Regions, Genetic
  • Nucleic Acid Conformation
  • Models, Molecular
  • Genes, Bacterial
 

Citation

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Schumacher, M. A., den Hengst, C. D., Bush, M. J., Le, T. B. K., Tran, N. T., Chandra, G., … Buttner, M. J. (2018). The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development. Nat Commun, 9(1), 1139. https://doi.org/10.1038/s41467-018-03576-3
Schumacher, Maria A., Chris D. den Hengst, Matthew J. Bush, T. B. K. Le, Ngat T. Tran, Govind Chandra, Wenjie Zeng, Brady Travis, Richard G. Brennan, and Mark J. Buttner. “The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development.Nat Commun 9, no. 1 (March 19, 2018): 1139. https://doi.org/10.1038/s41467-018-03576-3.
Schumacher MA, den Hengst CD, Bush MJ, Le TBK, Tran NT, Chandra G, et al. The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development. Nat Commun. 2018 Mar 19;9(1):1139.
Schumacher, Maria A., et al. “The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development.Nat Commun, vol. 9, no. 1, Mar. 2018, p. 1139. Pubmed, doi:10.1038/s41467-018-03576-3.
Schumacher MA, den Hengst CD, Bush MJ, Le TBK, Tran NT, Chandra G, Zeng W, Travis B, Brennan RG, Buttner MJ. The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development. Nat Commun. 2018 Mar 19;9(1):1139.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

March 19, 2018

Volume

9

Issue

1

Start / End Page

1139

Location

England

Related Subject Headings

  • Streptomyces coelicolor
  • Static Electricity
  • Repressor Proteins
  • Repetitive Sequences, Nucleic Acid
  • Regulon
  • Protein Structure, Quaternary
  • Promoter Regions, Genetic
  • Nucleic Acid Conformation
  • Models, Molecular
  • Genes, Bacterial