The Fadr DNA complex - Transcriptional control of fatty acid metabolism inEscherichia coli

In Escherichia coli, the expression of fatty acid metabolic genes is contro lled by the transcription factor, FadR, The affinity of FadR for DNA is con trolled by long chain acyl-CoA molecules, which bind to the protein and mod ulate gene expression. The crystal structure of FadR reveals a two domain d imeric molecule where the N-terminal domains bind DNA, and the C-terminal d omains bind 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 specifical ly recognizes a palindromic sequence. Structural and functional similaritie s to the Tet repressor and the BmrR transcription factors suggest how the b inding of the acyl-CoA effector molecule to the C-terminal domain may affec t the DNA binding affinity of the N-terminal domain. We suggest that the bi nding of acyl-CoA disrupts a buried network of charged and polar residues i n the C-terminal domain, and the resulting conformational change is transmi tted to the N-terminal domain via a domain-spanning alpha -helix.