Mechanism of environmentally driven conformational changes that modulate H-NS DNA bridging activity
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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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.
Copyright
© 2017, van der Valk et al.
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.
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