W0005

The FadR-DNA Complex: Transcriptional Control of Fatty Acid Metabolism in Escherichia coli. Yibin Xu^‡, Richard J. Heath^†, Zhenmei Li^‡, Charles O. Rock^† and Stephen W. White^‡

Departments of ^‡Structural Biology and ^†Biochemistry, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38105 Fax: 901-495-3032 E-mail: yibin.xu@stjude.org.

In Escherichia coli, the expression of fatty acid metabolic genes is controlled by a single transcription factor, FadR. The affinity of FadR for DNA is controlled by long chain acyl-CoA molecules which bind to the protein and modulate gene expression. The crystal structure of FadR reveals a two-domain dimeric molecule where the N-terminal domain binds DNA and the C-terminal domain binds acyl-CoA. The DNA-binding domain has a winged-helix motif, and the C-terminal domain resembles the sensor domain of the Tet repressor. The FadR-DNA complex reveals how the protein interacts with DNA and specifically recognizes a palindromic sequence. Structural and functional similarities to the Tet repressor and the BmrR transcription factors suggest how the binding of the acyl-CoA effector molecule to the C-terminal domain affects the DNA-binding affinity of the N-terminal domain. We suggest that the binding of acyl-CoA disrupts a buried network of charged and polar residues in the C-terminal domain, and the resulting conformational change is transmitted to the N-terminal domain via a domain-spanning (-helix.