title: Specific recognition between intrinsically disordered LEF and DNA.
abstract: Lymphoid enhancer-binding factor-1 (LEF-1) is a sequence-specific and cell type-specific transcription factor in regulation of the human T cell receptor α enhancer. It has been shown the minor groove of DNA can bind the intrinsic disordered LEF. To get an insight into the mechanism of how the intrinsic disordered LEF specifically recognizes DNA, we have performed explicit-solvent multiple molecular dynamics (MD) simulations to study the specific recognition between DNA and LEF. Room-temperature MD simulations suggest that the disordered C-tails of LEF have nonspecific and specific interactions with the minor groove of DNA. Kinetic analysis of high-temperature MD simulations shows that bound and apo-states unfold via a two-state process. The specific binding of the disordered C-tails of LEF can accelerate the formation of a complex. Gly38Ala and Met11Gly mutant simulations show that electrostatic interactions between DNA and LEF significantly decrease. Kolmogorov-Smirnov (KS) P test analysis illustrates that the specific recognition between DNA and LEF might follow an induced-fit mechanism. Furthermore, these methods can be used for the research of specific recognition between DNA and other intrinsic disordered proteins.
authors.affiliation: State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qin
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Chen
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding; D013696:Temperature
chemical_list: D051821:Lymphoid Enhancer-Binding Factor 1; D004247:DNA