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Nucleic Acids Res. 2019 Jun 4;47(10):5429-5435. doi: 10.1093/nar/gkz291.

Conformational tuning of a DNA-bound transcription factor.

Author information

1
Univ. Lille, CNRS, UMR 8516 - LASIR - Laboratoire de Spectrochimie Infrarouge et Raman, F-59000 Lille, France.
2
University Vienna, Department for Structural and Computational Biology, Max F. Perutz Laboratories, Campus Vienna BioCenter 5, 1030 Vienna, Austria.
3
Laboratoire des biomolécules, LBM, Département de chimie, École normale supérieure, PSL University, Sorbonne Université, CNRS, 75005 Paris, France.
4
University of Vienna, Faculty of Chemistry, Institute of Biological Chemistry, Währinger Str. 38, 1090 Vienna, Austria.

Abstract

Transcription factors are involved in many cellular processes that take place remote from their cognate DNA sequences. The efficiencies of these activities are thus in principle counteracted by high binding affinities of the factors to their cognate DNAs. Models such as facilitated diffusion or dissociation address this apparent contradiction. We show that the MYC associated transcription factor X (MAX) undergoes nanoscale conformational fluctuations in the DNA-bound state, which is consistent with facilitated dissociation from or diffusion along DNA strands by transiently reducing binding energies. An integrative approach involving EPR, NMR, crystallographic and molecular dynamics analyses demonstrates that the N-terminal domain of MAX constantly opens and closes around a bound DNA ligand thereby dynamically tuning the binding epitope and the mode of interaction.

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