Journal
EMBO JOURNAL
Volume 20, Issue 8, Pages 2041-2050Publisher
OXFORD UNIV PRESS
DOI: 10.1093/emboj/20.8.2041
Keywords
acyl-CoA; fatty acid; protein structure; regulation; transcription
Categories
Funding
- Wellcome Trust Funding Source: Medline
Ask authors/readers for more resources
FadR is an acyl-Coh-responsive transcription factor, regulating fatty acid biosynthetic and degradation genes in Escherichia coli, The ape-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 Angstrom 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 Angstrom, The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 Angstrom in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available