Mechanism of environmentally driven conformational changes that modulate H-NS DNA bridging activity

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Abstract

Bacteria frequently need to adapt to altered environmental conditions. Adaptation requires changes in gene expression, often mediated by global regulators of transcription. The nucleoid-associated protein H‑NS is a key global regulator in Gram-negative bacteria, and is believed to be a crucial player in bacterial chromatin organization via its DNA bridging activity. H‑NS activity in vivo is modulated by physico-chemical factors (osmolarity, pH, temperature) and interaction partners.Mechanistically it is unclear how functional modulation of H-NS by such factors is achieved. Here, we show that a diverse spectrum of H-NS modulators alter the DNA bridging activity of H-NS. Changes in monovalent and divalent ion concentrations drive an abrupt switch between a bridging and non-bridging DNA binding mode. Similarly, synergistic and antagonistic co-regulators modulate the DNA bridging efficiency. Structural studies suggest a conserved mechanism: H-NS switches between a "closed" and an "open", bridging competent, conformation driven by environmental cues and interaction partners.

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Ramon A van der Valk

Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands

Competing interests
The authors declare that no competing interests exist.
Jocelyne Vreede

Computational Chemistry, van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, Netherlands

Competing interests
The authors declare that no competing interests exist.
Liang Qin

Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands

Competing interests
The authors declare that no competing interests exist.
Geri F Moolenaar

Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands

Competing interests
The authors declare that no competing interests exist.
Andreas Hofmann

Institute for Theoretical Physics, University of Heidelberg, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
Nora Goosen

Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands

Competing interests
The authors declare that no competing interests exist.
Remus T Dame

Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands

For correspondence
rtdame@chem.leidenuniv.nl

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9863-1692

Funding

NanonextNL of the Government of the Netherland and 130 partners

Ramon A van der Valk
Geri F Moolenaar
Remus T Dame

Netherlands Organisation for Scientific Research (VIDI 864.08.001)

Ramon A van der Valk
Geri F Moolenaar
Nora Goosen
Remus T Dame

Netherlands Organisation for Scientific Research (Athena grant 700.58.802)

Jocelyne Vreede

Human Frontier Science Program (RGP0014/2014)

Andreas Hofmann
Remus T Dame

China Scholarship Council (No. 201506880001)

Liang Qin

Netherlands Organisation for Scientific Research (VICI 016.160.613)

Remus T Dame

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.