title: One is not enough.
abstract: In both prokaryotic and eukaryotic organisms, repressors and activators are responsible for regulating gene expression. The lac operon is a paradigm for understanding how metabolites function as signaling molecules and modulate transcription. These metabolites or allosteric effector molecules bind to the repressor and alter the conformational equilibrium between the induced and the repressed states. Here, we describe a set of experiments where we modified a single inducer binding site in a dimeric repressor and examined its effect on induction. Based upon these observations, we have been able to calculate the thermodynamic parameters that are responsible for the allosteric properties that govern repressor function. Understanding how effector molecules alter the thermodynamic properties of the repressor is essential for establishing a detailed understanding of gene regulation.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 37th and Hamilton Walk, Philadelphia, PA 19104-6059, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Daber
authors.forename: Kim
authors.initials: K
authors.lastname: Sharp
authors.forename: Mitchell
authors.initials: M
authors.lastname: Lewis
mesh_terms: D000494:Allosteric Regulation; D019943:Amino Acid Substitution / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D019281:Dimerization; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D056968:Lac Repressors; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D012097:Repressor Proteins; D049452:Green Fluorescent Proteins