ACTIVATION OF GENE-EXPRESSION BY A LIGAND-INDUCED CONFORMATIONAL CHANGE OF A PROTEIN-DNA COMPLEX

IlvY protein binds cooperatively to tandem operator sites in the diver gent, overlapping, promoter-regulatory region of the ilvYC operon of E scherichia coli, IlvY positively regulates the expression of the ilvC gene in an inducer-dependent manner and negatively regulates the trans cription of its own divergently transcribed structural gene in an indu cer-independent manner. Although binding of IlvY protein to the tandem operators is sufficient to repress ilvY promoter-specific transcripti on, it is not sufficient to activate transcription from the ilvC promo ter. Activation of ilvC promoter-specific transcription requires the a dditional binding of a small molecule inducer to the IlvY protein-DNA complex. The binding of inducer to IlvY protein does not affect the af finity of IlvY protein for the tandem operator sites. It does, however , cause a conformational change of the IlvY protein-DNA complex, which is correlated with the partial relief of an IlvY protein-induced bend of the DNA helix in the ilvC promoter region, This structural change in the IlvY protein-DNA complex results in a 100-fold increase in the affinity of RNA polymerase binding at the ilvC promoter site. The abil ity of a protein to regulate gene expression by ligand-responsive modu lation of a protein-DNA structure is an emerging theme in gene regulat ion.