Comparing native and irradiated E. coli lactose repressor-operator complex by molecular dynamics simulation

• Published in: European biophysics journal 2010-09, Vol.39 (10), p.1375-1384
• Main Authors: Aci-Sèche, Samia, Garnier, Norbert, Goffinont, Stéphane, Genest, Daniel, Spotheim-Maurizot, Mélanie, Genest, Monique
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Binding sites; Binding Sites - physiology; Binding Sites - radiation effects; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Cell Biology; Deoxyribonucleic acid; Dihydroxyphenylalanine - chemistry; Dihydroxyphenylalanine - metabolism; Dihydroxyphenylalanine - radiation effects; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - metabolism; DNA, Bacterial - radiation effects; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - radiation effects; DNA-protein complex; E coli; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Escherichia coli Proteins - radiation effects; Gamma Rays; Hydrogen Bonding; Inactivation; Ionising radiation; Irradiation; Lac Repressors - chemistry; Lac Repressors - metabolism; Lac Repressors - radiation effects; Life Sciences; Membrane Biology; Models, Molecular; molecular dynamics; Molecular Dynamics Simulation; Molecular Sequence Data; Nanotechnology; Neurobiology; Operator Regions, Genetic; Original Paper; Oxidation; Oxidation-Reduction; Protein oxidation; Simulation; Static Electricity
• ISSN: 0175-7571; 1432-1017
• DOI: 10.1007/s00249-010-0591-1

The function of the E. coli lactose operon requires the binding of the tetrameric repressor protein to the operator DNA. We have previously shown that γ-irradiation destabilises the repressor-operator complex because the repressor gradually loses its DNA-binding ability (Radiat Res 170:604-612, 2008). It was suggested that the observed oxidation of tyrosine residues and the concomitant structural changes of irradiated headpieces (DNA-binding domains of repressor monomers) could be responsible for the inactivation. To unravel the mechanisms that lead to repressor-operator complex destabilisation when tyrosine oxidation occurs, we have compared by molecular dynamic simulations two complexes: (1) the native complex formed by two headpieces and the operator DNA, and (2) the damaged complex, in which all tyrosines are replaced by their oxidation product 3,4-dihydroxyphenylalanine (DOPA). On a 20 ns time scale, MD results show effects consistent with complex destabilisation: increased flexibility, increased DNA bending, modification of the hydrogen bond network, and decrease of the positive electrostatic potential at the protein surface and of the global energy of DNA-protein interactions.