17 Molecular Characteristics of the Regulatory Switch in Phages 434 and λ

Abstract

OVERVIEW
The dimeric repressor and Cro proteins of temperate bacteriophages λ and 434 recognize operator sites with approximate twofold symmetry. Each protein monomer is anchored on its half-site by a set of positioning contacts that include hydrogen bonds to DNA phosphates. Base pairs in the outer parts of the operator are specified by interactions with side chains on the recognition helix of the helix-turn-helix motif. Base pairs near the center of the operator are specified in λ by a second recognition element, the amino-terminal arm, and in 434 by the effects of sequence on DNA conformability. Differences between repressor and Cro that are important for differential recognition are distributed; they are not restricted to one or a few side chains that contact bases directly.

INTRODUCTION
The temperate bacteriophages related to λ can switch from lysogeny to lytic growth in response to induction by UV irradiation and other stimuli (Lwoff 1953). Two proteins, repressor and Cro, and two major operators, O_R and O_L, govern the immediate molecular mechanism of this decision (see references in Johnson et al. 1981; Ptashne 1986). Each operator has three sites, all of which bind both proteins. A critical characteristic of O_R (Fig. 1) is that repressor binds most tightly to site O_R1 and least tightly to site O_R3, whereas Cro has opposite relative affinities. Occupancy of O_R1 represses transcription from promoter P_R; occupancy of O_R3 represses transcription from P_RM. Thus, the presence of repressor maintains lysogeny by inactivating lytic functions transcribed from P_R and controls its...