Molecular flexibility in protein-DNA interactions.

In living cells protein-DNA interactions are fundamental processes. Here, we compare the 3D structures of several DNA-binding proteins frequently determined with and without attached DNA. We studied the global structure (backbone-traces) as well as the local structure (binding sites) by comparing pair-wise the related atoms. The DNA-interaction sites of uncomplexed proteins show conspicuously high local structural flexibility. Binding to DNA results in specific local conformations, which are clearly distinct from the unbound states. The adaptation of the protein's binding site to DNA can never be described by the lock and key model but in all cases by the induced fit model. Conformational changes in the seven protein backbone traces take place in different ways. Two of them dock onto DNA without a significant change, while the other five proteins are characterized by a backbone conformation change caused by DNA docking. In the case of three proteins of the latter group the DNA-complexed conformation also occurs in a few uncomplexed structures. This behavior can be described by a conformational ensemble, which is narrowed down by DNA docking until only one single DNA-complexed conformation occurs. Different docking models are discussed and each of the seven proteins is assigned to one of them.