Lrp, a global regulatory protein of Escherichia coli, binds co-operatively to multiple sites and activates transcription of ilvIH.

Lrp (Leucine-responsive regulatory protein) has recently been recognized as a major regulatory protein that controls the expression of many operons in Escherichia coli. Footprinting and gel retardation experiments with DNA from ilvIH, one of the operons controlled positively by Lrp, indicate that Lrp binds to six sites over a 200 base-pair region upstream from the promoter. Binding of Lrp to some of these sites is highly co-operative. We suggest a consensus sequence for Lrp binding based upon a comparison of six binding sites. An analysis of mutants indicates that five out of six binding sites are important for transcription activation and that two or three adjacent Lrp binding sites act synergistically in vivo. The observed synergistic effects in vivo may result from co-operative binding of Lrp to adjacent sites. We propose a model in which multiple binding sites contribute to the formation of a nucleoprotein complex, but only a particular proximal site positions Lrp properly so that it interacts with RNA polymerase.