Biological innovation in the functional landscape of a model regulator, or the lactose operon repressor

The operon model was proposed six decades ago. And yet, despite all this time, the lactose operon repressor, LacI, remains a subject of major interest. While it is well established that LacI can exist in two functional forms, one that renders the operon inactive via binding of LacI to DNA and another, bound to an inducer that does not allow repression, how it switches from one to the other is still not well understood. The construction of a library of several tens of thousands of LacI mutants has revealed some unexpected features. In particular, the transition implemented in some of them reveals a new type of transcription regulation: band-pass (OFF/ON/OFF) and band-stop (ON/OFF/ON) filters. This makes it natural to think that it is the network of hydrogen bonds associated with the water bound to the molecule that allows the remote interconnection between the binding site to an inducer molecule and the one that binds it to the DNA.