Role of DNA Binding Linked Protein-Protein Interactions in Gene Regulation

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9513661 Senear Sequence specific binding of regulatory proteins to unique DNA sites is the basis for regulation of transcriptional initiation. These studies are involved with the roles of protein-protein interactions in mediating these processes. One aim is to determine how dimer self-assembly and coupled interactions mediate DNA binding cooperativity. Dimers can self-assemble in solution to form octamers as the immediate product. Tetramers, the species long believed to mediate pairwise cooperativity, are minor intermediates in a concerted reaction. Therefore, coupled interactions are responsible for selecting a minor component of the solution species distribution as a major component of the DNA-bound distribution, hence as critical to regulation. By investigating the thermodynamic cycles that couple repressor self-assembly to operator binding, one can determine what solution assembly contributes to cooperativity and what protein and DNA mediated coupling contribute. A second aim addresses how protein-protein interactions contribute to differential affinity of repressor dimers for the three OR operator sites. It is now well established that the separate subunits that bind the two halves of the pseudo-palindromic operators do not interact independently with DNA. Coupling between the individual subunit-half site interactions involves both repressor and DNA conformational changes. Correlating structural and chemical changes resulting in the dimer interface with effects on dimer stability and operator binding specificity will lead to an understanding of the mechanisms of inter-subunit communication and protein structural changes that contribute to differential operator affinity. ***