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.

Lactose repressor hinge domain independently binds DNA

“…Results of DNA binding experiments for these constructs indicate that the hinge region mediates both specific and nonspecific binding, with only small differences in affinity for these targets and no impact of inducer binding. These data are consistent with NMR analysis and with theoretical predictions that the hinge region contributes to both operator and nonspecific DNA binding …”

“…Xu and colleagues have used molecular dynamics simulations and correlation network analysis to examine the recognition of DNA sequences by LacI. Electrostatic and hydrogen‐bonding interactions were found to be prominent in mediating nonspecific interaction with DNA.…”

“…In contrast, high‐affinity operator binding relied on hydrophobic interactions by the hinge helices that introduce the bending required for specific interaction with operator DNA sequences. Xu et al . concluded that the hinge region played an important role in modulating information flow between LacI and DNA sites.…”

“…Note that this region is not observed in crystallographic structures in the absence of operator DNA nor in the presence of inducer . However, NMR structural data and recent theoretical/computational studies by Xu et al . and Sun et al .…”

Secondary structures transition of tau protein with intrinsically disordered proteins specific force field

“…[65][66][67][68][69] In our study, the correlations were stored as a covariance matrix and the correlation-based networks for Tau(267-312) were constructed with 2 ps per snapshot. There were several systems of the successful application of this general method.…”