Conformational changes of the Tet repressor induced by tetracycline trapping

J Mol Biol. 1998 Jun 5;279(2):439-47. doi: 10.1006/jmbi.1998.1775.


The X-ray crystal structure analysis of inducer-free Tet repressor, TetR, at 2.4 A resolution identifies one of two openings of the tunnel-like binding site as the entrance for the inducer tetracycline-Mg2+, [Mg Tc]+. Recognition and binding of the inducer unleashes conformational changes leading to the induced state of TetR. In the first step, the C-terminal turn of alpha-helix 6 unwinds, thereby altering the orientation of alpha-helix 4. This different orientation of alpha-helix 4 is stabilized by a series of hydrogen bonds mediated through a chain of eight water molecules. The alpha-helix 4 connects the DNA-binding domain (alpha-helices 1 to 3) to the rigid TetR core, and thus regulates gene expression through its respective orientations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Binding Sites
  • Crystallography, X-Ray
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Gene Expression Regulation, Bacterial
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Conformation
  • Protein Structure, Secondary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Tetracycline / chemistry*
  • Water / chemistry


  • Bacterial Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • tetracycline resistance-encoding transposon repressor protein
  • Water
  • Tetracycline