title: Recognition mechanism between Lac repressor and DNA with correlation network analysis.
abstract: Lac repressor is a DNA-binding protein which inhibits the expression of a series of genes involved in lactose metabolism. Lac repressor can bind at a random DNA site via nonspecific interactions; then, it rapidly translocates through the double chain of DNA until it finds the specific binding site. Therefore, the site transform between these two modes is essential for the specific recognition between Lac repressor and DNA. Here, the recognition mechanism between Lac repressor and DNA was illustrated with molecular dynamics simulations and correlation network analyses. We have found that the correlation network of the specific system (2KEI) is more centralized and denser than that of the nonspecific system (1OSL). The significant difference in the networks between the nonspecific and specific systems is apparently due to the different binding modes. Then, different interaction modes were found where electrostatic and hydrogen bonding interactions in the nonspecific system are stronger than those in the specific system. Hydrophobic interactions were found only in specific complexes and mostly focused on the hinge helices. Furthermore, the hinge helix will induce the bending of DNA for the specific system. At the same time, a common specific sequence of DNA was revealed for three specific systems. Then, two design systems (positive and control) were used to evaluate the specific recognition between DNA and Lac repressor. These combined methods can be used to reveal the recognition mechanism between other transcription factors and DNA.
authors: State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University , 800 Dongchuan Road, Shanghai, 200240, China.
authors: Lishi
authors: L
authors: Xu
authors: Wei
authors: W
authors: Ye
authors: Cheng
authors: C
authors: Jiang
authors: Jingxu
authors: J
authors: Yang
authors: Jinmai
authors: J
authors: Zhang
authors: Yan
authors: Y
authors: Feng
authors: Ray
authors: R
authors: Luo
authors: Hai-Feng
authors: HF
authors: Chen
mesh_terms: D004247:DNA / Q000378:metabolism*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056968:Lac Repressors / Q000235:genetics / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D025341:Principal Component Analysis; D055672:Static Electricity
chemical_list: D056968:Lac Repressors; D004247:DNA