Crystal Structure of the Lactose Operon Repressor and Its Complexes with DNA and Inducer

• Published in: Science (American Association for the Advancement of Science) Vol. 271; no. 5253; pp. 1247 - 1254
• Main Authors: Lewis, Mitchell, Chang, Geoffrey, Horton, Nancy C., Kercher, Michele A., Pace, Helen C., Schumacher, Maria A., Brennan, Richard G., Lu, Ponzy
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 01.03.1996; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Algorithms; Allosteric Regulation; Analytical, structural and metabolic biochemistry; Atoms; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Base Sequence; Binding and carrier proteins; Binding Sites; Biological and medical sciences; Coding; Crystallography, X-Ray; Crystals; Cyclic AMP Receptor Protein - metabolism; Deoxyribonucleic acid; Dimers; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - metabolism; Electrical phases; Electron density; Escherichia coli; Escherichia coli Proteins; Fundamental and applied biological sciences. Psychology; Genetic regulation; Genetics; Hydrogen Bonding; Isopropyl Thiogalactoside - metabolism; Lac Operon; Lac Repressors; Mathematics; Models, Molecular; Molecular Biology; Molecular genetics; Molecular Sequence Data; Molecules; Monomers; Nucleic Acid Conformation; Operator Regions, Genetic; Point Mutation; Protein Conformation; Protein Folding; Protein Structure, Secondary; Proteins; Repressor proteins; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - metabolism; Research Article; Scientific Concepts; Lactose; Molecular structure; Operon; Escherichia coli; DNA binding protein; Bacteria; Transcription repressor; Biological activity; Enterobacteriaceae; Conformation; Crystalline structure
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.271.5253.1247

The lac operon of Escherichia coli is the paradigm for gene regulation. Its key component is the lac repressor, a product of the lacI gene. The three-dimensional structures of the intact lac repressor, the lac repressor bound to the gratuitous inducer isopropyl-β-D-1-thiogalactoside (IPTG) and the lac repressor complexed with a 21-base pair symmetric operator DNA have been determined. These three structures show the conformation of the molecule in both the induced and repressed states and provide a framework for understanding a wealth of biochemical and genetic information. The DNA sequence of the lac operon has three lac repressor recognition sites in a stretch of 500 base pairs. The crystallographic structure of the complex with DNA suggests that the tetrameric repressor functions synergistically with catabolite gene activator protein (CAP) and participates in the quaternary formation of repression loops in which one tetrameric repressor interacts simultaneously with two sites on the genomic DNA.