Abstract

MarR (multiple antibiotic resistance repressor) family proteins are bacterial repressors that regulate transcription in response to a wide range of chemical signals. Although specific features of MarR family function have been described, the role of atomic motions in MarRs remains unexplored thus limiting insights into the evolution of allostery in this ubiquitous family of repressors. Here, we provide the first experimental evidence that internal dynamics play a crucial functional role in MarR proteins. Streptococcus pneumoniae AdcR (adhesin-competence repressor) regulates ZnII homeostasis and ZnII functions as an allosteric activator of DNA binding. ZnII coordination triggers a transition from somewhat independent domains to a more compact structure. We identify residues that impact allosteric activation on the basis of ZnII-induced perturbations of atomic motions over a wide range of timescales. These findings appear to reconcile the distinct allosteric mechanisms proposed for other MarRs and highlight the importance of conformational dynamics in biological regulation.

Data availability

NMR datasets were deposited in Biological Magnetic Resonance Bank. Representative data generated or analyzed during this study are included in the supporting files.

The following data sets were generated

Article and author information

Author details

  1. Daiana A Capdevila

    Department of Chemistry, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0500-1016
  2. Fidel Huerta

    Department of Chemistry, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Katherine A Edmonds

    Department of Chemistry, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. My Tra Le

    Department of Chemistry, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Hongwei Wu

    Department of Chemistry, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. David P Giedroc

    Department of Chemistry, Indiana University, Bloomington, United States
    For correspondence
    giedroc@indiana.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2342-1620

Funding

NIH Office of the Director (GM118157)

  • David P Giedroc

Pew Charitable Trusts (Latin American Fellowship)

  • Daiana A Capdevila

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

Reviewing Editor

  1. Lewis E Kay, University of Toronto, Canada

Version history

  1. Received: April 4, 2018
  2. Accepted: October 16, 2018
  3. Accepted Manuscript published: October 17, 2018 (version 1)
  4. Version of Record published: November 8, 2018 (version 2)

Copyright

© 2018, Capdevila 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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  1. Daiana A Capdevila
  2. Fidel Huerta
  3. Katherine A Edmonds
  4. My Tra Le
  5. Hongwei Wu
  6. David P Giedroc
(2018)
Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator
eLife 7:e37268.
https://doi.org/10.7554/eLife.37268

Share this article

https://doi.org/10.7554/eLife.37268

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