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EMBO J. 2001 Apr 17;20(8):2041-50.

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

Author information

  • 1Wellcome Trust Biocentre, Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK. dava@davapc1.bioch.dundee.ac.uk

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 A 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 A. The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 A in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.

PMID:
11296236
[PubMed - indexed for MEDLINE]
PMCID:
PMC125426
Free PMC Article

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