ATP– and ADP–DnaA protein, a molecular switch in gene regulation

DnaA protein functions by binding to asymmetric 9mer DNA sites, the DnaA boxes. ATP–DnaA and ADP–DnaA bind to 9mer DnaA boxes with equal affinity, but only ATP–DnaA protein binds in addition to an as yet unknown 6mer site, the ATP–DnaA box AGATCT, or a close match to it. ATP–DnaA protein binding to ATP–DnaA boxes is restricted to sites located in close proximity to DnaA boxes, suggesting that protein–protein interaction is required for its stabilization. We show that ATP–DnaA represses dnaA transcription much more efficiently than ADP–DnaA. DnaA is thus a regulatory molecule that, depending on the adenosine nucleotide bound, can bind to different sequences and thereby fulfill distinct functions.