Functional switches in transcription regulation; molecular mimicry and plasticity in protein-protein interactions.

Abstract

The pairwise interactions in which a protein participates can dictate the functional properties of the protein. Indeed, there are many biological regulatory processes in which protein function is orchestrated via exchange of one protein partner for another. Several transcription regulatory proteins that participate in functional switching have been identified and extensively studied. In the examination of the structural basis of the switch for four of these proteins, a common theme of mutually exclusive protein-protein interactions emerges. The ability of these proteins to utilize the same surface to form alternative interactions reflects a second characteristic of these systems of molecular mimicry. Finally, in two of the systems, plasticity in adoption of secondary structure is integral to the formation of alternative protein-protein interactions. Regulation of formation of the alternative parings occurs by a range of mechanisms. In the simplest systems, the outcome of the switch reflects the relative probability of encounter of one partner versus another. Alternatively, more complex mechanisms include regulation of protein availability and compartmentalization of protein partners.