A two-lane mechanism for selective biological ammonium transport

  1. Gordon Williamson
  2. Giulia Tamburrino
  3. Adriana Bizior
  4. Mélanie Boeckstaens
  5. Gaëtan Dias Mirandela
  6. Marcus Bage
  7. Andrei Pisliakov
  8. Callum M Ives
  9. Eilidh Terras
  10. Paul A Hoskisson
  11. Anna-Maria Marini
  12. Ulrich Zachariae  Is a corresponding author
  13. Arnaud Javelle  Is a corresponding author
  1. University of Strathclyde, United Kingdom
  2. University of Dundee, United Kingdom
  3. Université Libre de Bruxelles, Belgium

Abstract

The transport of charged molecules across biological membranes faces the dual problem of accommodating charges in a highly hydrophobic environment while maintaining selective substrate translocation. This has been the subject of a particular controversy for the exchange of ammonium across cellular membranes, an essential process in all domains of life. Ammonium transport is mediated by the ubiquitous Amt/Mep/Rh transporters that includes the human Rhesus factors. Here, using a combination of electrophysiology, yeast functional complementation and extended molecular dynamics simulations, we reveal a unique two-lane pathway for electrogenic NH4+ transport in two archetypal members of the family, the transporters AmtB from Escherichia coli and Rh50 from Nitrosomonas europaea. The pathway underpins a mechanism by which charged H+ and neutral NH3 are carried separately across the membrane after NH4+ deprotonation. This mechanism defines a new principle of achieving transport selectivity against competing ions in a biological transport process.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-5 and Table 2.

Article and author information

Author details

  1. Gordon Williamson

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Giulia Tamburrino

    School of Life Sciences, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Adriana Bizior

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Mélanie Boeckstaens

    Department of Molecular Biology, Université Libre de Bruxelles, Gosselies, Belgium
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1629-7403
  5. Gaëtan Dias Mirandela

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5871-6288
  6. Marcus Bage

    School of Life Sciences, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Andrei Pisliakov

    School of Life Sciences, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Callum M Ives

    School of Life Sciences, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0511-1220
  9. Eilidh Terras

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Paul A Hoskisson

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Anna-Maria Marini

    Department of Molecular Biology, Université Libre de Bruxelles, Gosselies, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  12. Ulrich Zachariae

    School of Life Sciences / School of Science and Engineering, University of Dundee, Dundee, United Kingdom
    For correspondence
    u.zachariae@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  13. Arnaud Javelle

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    For correspondence
    arnaud.javelle@strath.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3611-5737

Funding

Tenovus (S17-07)

  • Arnaud Javelle

Scottish Universities Physics Alliance (NA)

  • Ulrich Zachariae

Natural Environment Research Council (NE/M001415/1)

  • Paul A Hoskisson

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

Reviewing Editor

  1. Nir Ben-Tal, Tel Aviv University, Israel

Publication history

  1. Received: March 24, 2020
  2. Accepted: July 13, 2020
  3. Accepted Manuscript published: July 14, 2020 (version 1)
  4. Version of Record published: August 25, 2020 (version 2)
  5. Version of Record updated: January 27, 2022 (version 3)

Copyright

© 2020, Williamson 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. Gordon Williamson
  2. Giulia Tamburrino
  3. Adriana Bizior
  4. Mélanie Boeckstaens
  5. Gaëtan Dias Mirandela
  6. Marcus Bage
  7. Andrei Pisliakov
  8. Callum M Ives
  9. Eilidh Terras
  10. Paul A Hoskisson
  11. Anna-Maria Marini
  12. Ulrich Zachariae
  13. Arnaud Javelle
(2020)
A two-lane mechanism for selective biological ammonium transport
eLife 9:e57183.
https://doi.org/10.7554/eLife.57183
  1. Further reading

Further reading

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