title: The spacing between binding sites controls the mode of cooperative DNA-protein interactions: implications for evolution of regulatory circuitry.
abstract: The CI repressors of lambdoid phages bind cooperatively to adjacent binding sites. Although these binding sites are found at complex operators containing three binding sites, cooperative binding occurs only between dimers bound at two of the sites, a mode of binding termed pairwise cooperativity. At the level of regulation, pairwise cooperativity allows the proper operation of the genetic switch. At the mechanistic level, it has been proposed to result from steric distortion of the complex, such that a protein dimer bound to a central site cannot contact both flanking dimers because it "leans" towards one of the two sites. We have tested this model using the CI repressor of phage HK022. Previous work suggested that reducing the spacing between adjacent operators might allow cooperative interaction among three dimers, a mode of cooperativity we term extended. Using a set of synthetic templates, we have shown that reducing the spacing allows extended cooperativity among three binding sites. Accordingly, the mode of cooperativity changes qualitatively in response to changes in the inter-site spacing. That is, the change in spacing has major functional consequences for the properties of the complex. We suggest that such changes can play important roles in the evolution of gene regulatory circuitry and of other processes involving nucleoprotein complexes.
authors.affiliation: Department of Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: J W
authors.initials: JW
authors.lastname: Little
mesh_terms: D010582:Bacteriophage lambda / Q000378:metabolism*; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019143:Evolution, Molecular; D012097:Repressor Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; D004247:DNA