Chemical Structure and Functional Organization of lac Repressor from Escherichia coli

INTRODUCTION Jacob and Monod (1961) proposed in their operon model that control genes would make repressors which would turn off the structural genes. This was an act of turning away from the hitherto discussed instructive theories of control. The essential and also new idea put forward was that the repressor acts as an intermediate to make the connection between the signal provided by the inducer or corepressor molecules and the target for the control, the operator. The signal molecules bind to the repressor and alter its affinity for the operator. If we want to understand these interactions, we have to answer the question about the molecular nature and chemical structure of both elements. The isolations of nonsense mutations in the λ repressor C I gene (Jacob et al. 1962; Thomas and Lambert 1962) and in the lac repressor I gene (Bourgeois et al. 1965; Muller-Hill 1966) provided the first convincing genetic evidence for the nature of repressors. Suppression restored repressor activity and showed that the repressor genes encode proteins. The final proof was brought forth by Gilbert and Muller-Hill (1966) with the isolation of the lac repressor. They demonstrated that the repressor is a protein which binds β -D-galactosides in vitro and cosediments with lac operator DNA only in the absence of the gratuitous inducer isopropyl-1-thio- β -D-galactopyranoside (IPTG) (Gilbert and Muller-Hill 1966Gilbert and Muller-Hill 1967). The amount of repressor made by the haploid wild-type cell is very small. The intracellular concentration of lac repressor was estimated by Gilbert and Muller-Hill (1966) to be on the...