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Elife. 2017 Sep 26;6. pii: e27369. doi: 10.7554/eLife.27369.

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

Author information

1
Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands.
2
Computational Chemistry, Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, Netherlands.
3
Institute for Theoretical Physics, University of Heidelberg, Heidelberg, Germany.
4
Centre for Microbial Cell Biology, Leiden University, Leiden, Netherlands.

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.

KEYWORDS:

E. coli; H-NS; Hha; YdgT; bacterial chromatin; biophysics; chromosomes; genes; nucleoid; structural biology

PMID:
28949292
PMCID:
PMC5647153
DOI:
10.7554/eLife.27369
[Indexed for MEDLINE]
Free PMC Article

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