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

  1. Ramon A van der Valk
  2. Jocelyne Vreede
  3. Liang Qin
  4. Geri F Moolenaar
  5. Andreas Hofmann
  6. Nora Goosen
  7. Remus T Dame  Is a corresponding author
  1. Leiden University, Netherlands
  2. University of Amsterdam, Netherlands
  3. University of Heidelberg, Germany

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.

Article and author information

Author details

  1. Ramon A van der Valk

    Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. 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.
  3. Liang Qin

    Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Geri F Moolenaar

    Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Andreas Hofmann

    Institute for Theoretical Physics, University of Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Nora Goosen

    Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. 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.
    ORCID icon "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.

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.

Metrics

  • 2,878
    views
  • 511
    downloads
  • 94
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Ramon A van der Valk
  2. Jocelyne Vreede
  3. Liang Qin
  4. Geri F Moolenaar
  5. Andreas Hofmann
  6. Nora Goosen
  7. Remus T Dame
(2017)
Mechanism of environmentally driven conformational changes that modulate H-NS DNA bridging activity
eLife 6:e27369.
https://doi.org/10.7554/eLife.27369

Share this article

https://doi.org/10.7554/eLife.27369

Further reading

    1. Structural Biology and Molecular Biophysics
    Laura-Marie Silbermann, Benjamin Vermeer ... Katarzyna Tych
    Review Article

    Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of ‘clients’ (substrates). After decades of research, several ‘known unknowns’ about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases. We highlight three fundamental open questions, reviewing the current state of the field for each, and discuss new opportunities, including single-molecule technologies, to answer the known unknowns of the Hsp90 chaperone.

    1. Structural Biology and Molecular Biophysics
    Chuchu Wang, Chunyu Zhao ... Cong Liu
    Research Advance

    Previously, we reported that α-synuclein (α-syn) clusters synaptic vesicles (SV) Diao et al., 2013, and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering Lai et al., 2023. Meanwhile, post-translational modifications (PTMs) of α-syn such as acetylation and phosphorylation play important yet distinct roles in regulating α-syn conformation, membrane binding, and amyloid aggregation. However, how PTMs regulate α-syn function in presynaptic terminals remains unclear. Here, based on our previous findings, we further demonstrate that N-terminal acetylation, which occurs under physiological conditions and is irreversible in mammalian cells, significantly enhances the functional activity of α-syn in clustering SVs. Mechanistic studies reveal that this enhancement is caused by the N-acetylation-promoted insertion of α-syn’s N-terminus and increased intermolecular interactions on the LPC-containing membrane. N-acetylation in our work is shown to fine-tune the interaction between α-syn and LPC, mediating α-syn’s role in synaptic vesicle clustering.