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 journalArticle

112 Scopus citations

Abstract

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
Volume20
Issue number8
DOIs
StatePublished - Apr 17 2001

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Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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