The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR

Daan M.F. Van Aalten, Concetta C. DiRusso, Jens Knudsen

Research output: Contribution to journalArticlepeer-review

135 Scopus citations


FadR is an acyl-CoA-responsive transcription factor, regulating fatty acid biosynthetic and degradation genes in Escherichia coli. The apo-protein binds DNA as a homodimer, an interaction that is disrupted by binding of acyl-CoA. The recently described structure of apo-FadR shows a DNA binding domain coupled to an acyl-CoA binding domain with a novel fold, but does not explain how binding of the acyl-CoA effector molecule >30 Å away from the DNA binding site affects transcriptional regulation. Here, we describe the structures of the FadR-operator and FadR-myristoyl-CoA binary complexes. The FadR-DNA complex reveals a novel winged helix-turn-helix protein-DNA interaction, involving sequence-specific contacts from the wing to the minor groove. Binding of acyl-CoA results in dramatic conformational changes throughout the protein, with backbone shifts up to 4.5 Å. The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 Å in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.

Original languageEnglish (US)
Pages (from-to)2041-2050
Number of pages10
JournalEMBO Journal
Issue number8
StatePublished - Apr 17 2001
Externally publishedYes


  • Acyl-CoA
  • Fatty acid
  • Protein structure
  • Regulation
  • Transcription

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


Dive into the research topics of 'The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR'. Together they form a unique fingerprint.

Cite this