3 Protein-Protein Interactions and DNA Loop Formation

Abstract

I. INTRODUCTION
Recent studies of a number of prokaryotic operons have revealed that regulatory proteins bound at widely separated sites on the DNA can interact, thereby inducing the formation of a DNA loop. Such loops appear to play a critical role in the transcriptional regulation of several of these operons. DNA loop formation was first implicated in the regulation of the galactose and arabinose operons of Escherichia coli. In both cases, transcriptional repression was found to depend on operator sites located at considerable distances from the promoter regions, leading to the suggestion that repression was mediated by an interaction between repressors bound at widely separated sites.

This chapter will begin with a description of a model system for studying DNA loop formation, the binding of λ repressor to artificially separated operator sites. This will be followed by a qualitative discussion of the energetics of loop formation. The last section will contain a review of several prokaryotic systems in which loop formation has been studied.

II. DNA LOOP FORMATION BY λ REPRESSOR
λ repressor binds cooperatively to adjacent operators on the phage chromosome (Johnson et al. 1979). That is, the presence of a strong repressor binding site adjacent to a weaker site increases the affinity of the weaker site for repressor. Consider, for example, the interaction of λ repressor with the right operator (O_R) in a λ lysogen (see Fig. 1a) (for review, see Ptashne 1986a). O_R1 binds repressor relatively tightly, whereas O_R2 and O_R3 each have an intrinsically weaker affinity...