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Structures of carbon catabolite protein A-(HPr-Ser46-P) bound to diverse catabolite response element sites reveal the basis for high-affinity binding to degenerate DNA operators.

Publication ,  Journal Article
Schumacher, MA; Sprehe, M; Bartholomae, M; Hillen, W; Brennan, RG
Published in: Nucleic Acids Res
April 2011

In Gram-positive bacteria, carbon catabolite protein A (CcpA) is the master regulator of carbon catabolite control, which ensures optimal energy usage under diverse conditions. Unlike other LacI-GalR proteins, CcpA is activated for DNA binding by first forming a complex with the phosphoprotein HPr-Ser46-P. Bacillus subtilis CcpA functions as both a transcription repressor and activator and binds to more than 50 operators called catabolite response elements (cres). These sites are highly degenerate with the consensus, WTGNNARCGNWWWCAW. How CcpA-(HPr-Ser46-P) binds such diverse sequences is unclear. To gain insight into this question, we solved the structures of the CcpA-(HPr-Ser46-P) complex bound to three different operators, the synthetic (syn) cre, ackA2 cre and gntR-down cre. Strikingly, the structures show that the CcpA-bound operators display different bend angles, ranging from 31° to 56°. These differences are accommodated by a flexible linkage between the CcpA helix-turn-helix-loop-helix motif and hinge helices, which allows independent docking of these DNA-binding modules. This flexibility coupled with an abundance of non-polar residues capable of non-specific nucleobase interactions permits CcpA-(HPr-Ser46-P) to bind diverse operators. Indeed, biochemical data show that CcpA-(HPr-Ser46-P) binds the three cre sites with similar affinities. Thus, the data reveal properties that license this protein to function as a global transcription regulator.

Duke Scholars

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

April 2011

Volume

39

Issue

7

Start / End Page

2931 / 2942

Location

England

Related Subject Headings

  • Transcription Factors
  • Response Elements
  • Protein Binding
  • Phosphoproteins
  • Operator Regions, Genetic
  • Models, Molecular
  • Developmental Biology
  • DNA-Binding Proteins
  • DNA, Bacterial
  • Crystallography, X-Ray
 

Citation

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Schumacher, M. A., Sprehe, M., Bartholomae, M., Hillen, W., & Brennan, R. G. (2011). Structures of carbon catabolite protein A-(HPr-Ser46-P) bound to diverse catabolite response element sites reveal the basis for high-affinity binding to degenerate DNA operators. Nucleic Acids Res, 39(7), 2931–2942. https://doi.org/10.1093/nar/gkq1177
Schumacher, Maria A., Mareen Sprehe, Maike Bartholomae, Wolfgang Hillen, and Richard G. Brennan. “Structures of carbon catabolite protein A-(HPr-Ser46-P) bound to diverse catabolite response element sites reveal the basis for high-affinity binding to degenerate DNA operators.Nucleic Acids Res 39, no. 7 (April 2011): 2931–42. https://doi.org/10.1093/nar/gkq1177.
Schumacher, Maria A., et al. “Structures of carbon catabolite protein A-(HPr-Ser46-P) bound to diverse catabolite response element sites reveal the basis for high-affinity binding to degenerate DNA operators.Nucleic Acids Res, vol. 39, no. 7, Apr. 2011, pp. 2931–42. Pubmed, doi:10.1093/nar/gkq1177.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

April 2011

Volume

39

Issue

7

Start / End Page

2931 / 2942

Location

England

Related Subject Headings

  • Transcription Factors
  • Response Elements
  • Protein Binding
  • Phosphoproteins
  • Operator Regions, Genetic
  • Models, Molecular
  • Developmental Biology
  • DNA-Binding Proteins
  • DNA, Bacterial
  • Crystallography, X-Ray