Functional rules for lac repressor–operator associations and implications for protein–DNA interactions

The Lac repressor has been used as a tool to understand protein-DNA recognition for many years. Recent experiments have demonstrated the ability of the Lac repressor to control gene expression in various eukaryotic systems, making the quest for an arsenal of protein-DNA binding partners desirable for potential therapeutic applications. Here, we present the results of the most exhaustive screen of Lac repressor-DNA binding partners to date, resulting in the elucidation of functional rules for Lac-DNA binding. Even within the confines of a single protein-DNA scaffold, modes of binding of different protein-DNA partners are sufficiently diverse so as to prevent elucidation of generalized rules for recognition for a single protein, much less an entire protein family.