期刊
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
卷 20, 期 -, 页码 5264-5274出版社
ELSEVIER
DOI: 10.1016/j.csbj.2022.09.020
关键词
DNA supercoiling; DNA -protein recognition; Indirect readout; Molecular Dynamics Simulations
资金
- Engineering and Physical Sciences Research Council (EPSRC) [EP/N027639/1, EP/T002166/1, EP/R029407/1, EP/P020259/1]
- Biology and Biotechnology Research Council (BBSRC) [BB/R001235/1]
- Leverhulme Trust [RPG-2017-340]
- University of York Research Priming funds [50109436, G0081301]
- York Open Access Fund
Using molecular dynamics simulations on DNA minicircles, this study reveals the reciprocal influence between a DNA-bending protein (IHF) and DNA supercoiling. Supercoiled DNA enhances wrapping around IHF, while IHF acts as a "supercoiling relief" factor by compacting relaxed DNA loops and pinning the position of plectonemes in a unique manner. IHF also restrains DNA torsion and divides DNA into independent topological domains through bridging.
The integration host factor (IHF) is a prominent example of indirect readout as it imposes one of the strongest bends on relaxed linear DNA. However, the relation between IHF and torsionally constrained DNA, as occurs physiologically, remains unclear. By using atomistic molecular dynamics simulations on DNA minicircles, we reveal, for the first time, the reciprocal influence between a DNA-bending protein and supercoiling. On one hand, the increased curvature of supercoiled DNA enhances wrapping around IHF making the final complex topologically dependent. On the other hand, IHF acts as a 'supercoiling relief' factor by compacting relaxed DNA loops and, when supercoiled, it pins the position of plectonemes in a unique and specific manner. In addition, IHF restrains under- or overtwisted DNA depending on whether the complex is formed in negatively or positively supercoiled DNA, becoming effectively a 'supercoiling buffer'. We finally provide evidence of DNA bridging by IHF and reveal that these bridges divide DNA into independent topological domains. We anticipate that the crosstalk detected here between the 'active' DNA and the multifaceted IHF could be common to other DNA-protein complexes relying on the deformation of DNA.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
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