Affiliation:
1. Department of Life Sciences Presidency University Kolkata West Bengal India
Abstract
AbstractSpecific interactions between transcription factors (TFs) and substrate DNA constitute the fundamental basis of gene expression. Unlike in TFs like basic helix‐loop‐helix or basic leucine zippers, prediction of substrate DNA is extremely challenging for helix‐turn‐helix (HTH). Experimental techniques like chromatin immunoprecipitation combined with massively parallel DNA sequencing remains a viable option. We characterize the molecular basis of heterogeneity in HTH‐DNA interaction using in silico tools and thence validate them experimentally. Given the profound functional diversity in HTH, we focus primarily on winged‐HTH (wHTH). We consider 180 wHTH TFs, whose experimental three‐dimensional structures are available in DNA bound/unbound conformations. Starting with PDB‐wide scanning and curation of data, we construct a phylogenetic tree, which distributes 180 wHTH sequences under multiple sub‐groups. Structure‐sequence alignment followed by detailed intra/intergroup analysis, covariation studies and extensive network theory analysis help us to gain deep insight into heterogeneous wHTH‐substrate DNA interactions. A central aim of this study is to find a consensus to predict the substrate DNA sequence for wHTH, amidst heterogeneity. The strength of our exhaustive theoretical investigations including molecular docking are successfully tested through experimental characterization of wHTH TF from Sulfurimonas denitrificans.
Funder
Department of Biotechnology, Ministry of Science and Technology, India
Department of Science and Technology, Government of West Bengal
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
2 articles.
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