Regulation of the Dha operon of Lactococcus lactis: a deviation from the rule followed by the Tetr family of transcription regulators

J Biol Chem. 2006 Aug 11;281(32):23129-37. doi: 10.1074/jbc.M603486200. Epub 2006 Jun 7.

Abstract

Dihydroxyacetone (Dha) kinases are a novel family of kinases with signaling and metabolic functions. Here we report the x-ray structures of the transcriptional activator DhaS and the coactivator DhaQ and characterize their function. DhaQ is a paralog of the Dha binding Dha kinase subunit; DhaS belongs to the family of TetR repressors although, unlike all known members of this family, it is a transcriptional activator. DhaQ and DhaS form a stable complex that in the presence of Dha activates transcription of the Lactococcus lactis dha operon. Dha covalently binds to DhaQ through a hemiaminal bond with a histidine and thereby induces a conformational change, which is propagated to the surface via a cantilever-like structure. DhaS binding protects an inverted repeat whose sequence is GGACACATN6ATTTGTCC and renders two GC base pairs of the operator DNA hypersensitive to DNase I cleavage. The proximal half-site of the inverted repeat partially overlaps with the predicted -35 consensus sequence of the dha promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Deoxyribonuclease I / chemistry
  • Histidine / chemistry
  • Lactococcus lactis / metabolism*
  • Models, Genetic
  • Molecular Sequence Data
  • Operon
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Conformation
  • Repressor Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Transcription, Genetic*

Substances

  • Repressor Proteins
  • tetracycline resistance-encoding transposon repressor protein
  • Histidine
  • Phosphotransferases (Alcohol Group Acceptor)
  • glycerone kinase
  • Deoxyribonuclease I

Associated data

  • PDB/2IU4
  • PDB/2IU5
  • PDB/2IU6