Transcription activation by Escherichia coli FNR protein: similarities to, and differences from, the CRP paradigm

During transcription activation at FNR-dependent promoters where the DNA site for FNR overlaps the -35 element, a surface-exposed activating region in the upstream subunit of the FNR dimer interacts with the C-terminal domain of the RNA polymerase alpha subunit. Starting with a cloned fnr gene encoding a defective FNR derivative carrying substitutions in this activating region, we screened a library of random mutations to identify substitutions that restored FNR activity. Activity can be restored by substitutions at residues T118, E47 and K60. The locations of these residues identify three separate surface-exposed regions of FNR that can play a role in transcription activation. These three regions appear to be analogues of Activating Region 1, Activating Region 2 and Activating Region 3 of the cyclic AMP receptor protein, CRP: our results underscore the similarities between FNR and CRP.