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Issue 22, 2017
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Specific DNA sequences allosterically enhance protein–protein interaction in a transcription factor through modulation of protein dynamics: implications for specificity of gene regulation

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Abstract

Most genes are regulated by multiple transcription factors, often assembling into multi-protein complexes in the gene regulatory region. Understanding of the molecular origin of specificity of gene regulatory complex formation in the context of the whole genome is currently inadequate. A phage transcription factor λ-CI forms repressive multi-protein complexes by binding to multiple binding sites in the genome to regulate the lifecycle of the phage. The protein–protein interaction between two DNA-bound λ-CI molecules is stronger when they are bound to the correct pair of binding sites, suggesting allosteric transmission of recognition of correct DNA sequences to the protein–protein interaction interface. Exploration of conformation and dynamics by time-resolved fluorescence anisotropy decay and molecular dynamics suggests a change in protein dynamics to be a crucial factor in mediating allostery. A lattice-based model suggests that DNA-sequence induced allosteric effects could be crucial underlying factors in differentially stabilizing the correct site-specific gene regulatory complexes. We conclude that transcription factors have evolved multiple mechanisms to augment the specificity of DNA–protein interactions in order to achieve an extraordinarily high degree of spatial and temporal specificities of gene regulatory complexes, and DNA-sequence induced allostery plays an important role in the formation of sequence-specific gene regulatory complexes.

Graphical abstract: Specific DNA sequences allosterically enhance protein–protein interaction in a transcription factor through modulation of protein dynamics: implications for specificity of gene regulation

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Supplementary files

Article information


Submitted
22 Feb 2017
Accepted
11 May 2017
First published
26 May 2017

Phys. Chem. Chem. Phys., 2017,19, 14781-14792
Article type
Paper

Specific DNA sequences allosterically enhance protein–protein interaction in a transcription factor through modulation of protein dynamics: implications for specificity of gene regulation

A. Mazumder, S. Batabyal, M. Mondal, T. Mondol, S. Choudhury, R. Ghosh, T. Chatterjee, D. Bhattacharyya, S. K. Pal and S. Roy, Phys. Chem. Chem. Phys., 2017, 19, 14781
DOI: 10.1039/C7CP01193H

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