Feast/Famine regulation by transcription factor FL11 for the survival of the hyperthermophilic archaeon Pyrococcus OT3

Transcriptional repressor FL11 from the hyperthermophilic archaeon, Pyrococcus OT3, was crystallized in its dimer form in complex with a DNA duplex, TGAAA (WWW) under bar TTTCA. Chemical contacting of FL11 to the terminal 5 bps, and DNAbending by propeller twisting at (WWW) under bar confirmed specificity of the interaction. Dimer-binding sites were identified in promoters of similar to 200 transcription units coding, for example, H+-ATPase and NAD(P)H dehydrogenase. In the presence of lysine, four FL11 dimers were shown to assemble into an octamer, thereby covering the fl 11 promoter. In the feast mode, when P. OT3 grows on amino acids, the FL11 octamer will terminate transcription of fl11, as was shown in vitro, thereby derepressing transcription of many metabolic genes. In the famine mode in the absence of lysine, similar to 6000 FL11 dimers present per cell will arrest growth. This regulation resembles global regulation by Escherichia coli leucine-responsive regulatory protein, and hints at a prototype of transcription regulations now highly diverged.