IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0160219.html
   My bibliography  Save this article

Unveiling the Mechanism of Arginine Transport through AdiC with Molecular Dynamics Simulations: The Guiding Role of Aromatic Residues

Author

Listed:
  • Eva-Maria Krammer
  • Kassem Ghaddar
  • Bruno André
  • Martine Prévost

Abstract

Commensal and pathogenic enteric bacteria have developed several systems to adapt to proton leakage into the cytoplasm resulting from extreme acidic conditions. One such system involves arginine uptake followed by export of the decarboxylated product agmatine, carried out by the arginine/agmatine antiporter (AdiC), which thus works as a virtual proton pump. Here, using classical and targeted molecular dynamics, we investigated at the atomic level the mechanism of arginine transport through AdiC of E. coli. Overall, our MD simulation data clearly demonstrate that global rearrangements of several transmembrane segments are necessary but not sufficient for achieving transitions between structural states along the arginine translocation pathway. In particular, local structural changes, namely rotameric conversions of two aromatic residues, are needed to regulate access to both the outward- and inward-facing states. Our simulations have also enabled identification of a few residues, overwhelmingly aromatic, which are essential to guiding arginine in the course of its translocation. Most of them belong to gating elements whose coordinated motions contribute to the alternating access mechanism. Their conservation in all known E. coli acid resistance antiporters suggests that the transport mechanisms of these systems share common features. Last but not least, knowledge of the functional properties of AdiC can advance our understanding of the members of the amino acid-carbocation-polyamine superfamily, notably in eukaryotic cells.

Suggested Citation

  • Eva-Maria Krammer & Kassem Ghaddar & Bruno André & Martine Prévost, 2016. "Unveiling the Mechanism of Arginine Transport through AdiC with Molecular Dynamics Simulations: The Guiding Role of Aromatic Residues," PLOS ONE, Public Library of Science, vol. 11(8), pages 1-29, August.
  • Handle: RePEc:plo:pone00:0160219
    DOI: 10.1371/journal.pone.0160219
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160219
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0160219&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0160219?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yiling Fang & Hariharan Jayaram & Tania Shane & Ludmila Kolmakova-Partensky & Fang Wu & Carole Williams & Yong Xiong & Christopher Miller, 2009. "Structure of a prokaryotic virtual proton pump at 3.2 Å resolution," Nature, Nature, vol. 460(7258), pages 1040-1043, August.
    2. Harini Krishnamurthy & Chayne L. Piscitelli & Eric Gouaux, 2009. "Unlocking the molecular secrets of sodium-coupled transporters," Nature, Nature, vol. 459(7245), pages 347-355, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Saher Afshan Shaikh & Emad Tajkhorshid, 2010. "Modeling and Dynamics of the Inward-Facing State of a Na+/Cl− Dependent Neurotransmitter Transporter Homologue," PLOS Computational Biology, Public Library of Science, vol. 6(8), pages 1-14, August.
    2. Chunfeng Zhao & Sergei Yu Noskov, 2013. "The Molecular Mechanism of Ion-Dependent Gating in Secondary Transporters," PLOS Computational Biology, Public Library of Science, vol. 9(10), pages 1-12, October.
    3. Victoria C. Young & Hanayo Nakanishi & Dylan J. Meyer & Tomohiro Nishizawa & Atsunori Oshima & Pablo Artigas & Kazuhiro Abe, 2022. "Structure and function of H+/K+ pump mutants reveal Na+/K+ pump mechanisms," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Hyun Deok Song & Fangqiang Zhu, 2015. "Conformational Changes in Two Inter-Helical Loops of Mhp1 Membrane Transporter," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-19, July.
    5. Mary Hongying Cheng & Ivet Bahar, 2014. "Complete Mapping of Substrate Translocation Highlights the Role of LeuT N-terminal Segment in Regulating Transport Cycle," PLOS Computational Biology, Public Library of Science, vol. 10(10), pages 1-15, October.
    6. Jufang Shan & Jonathan A Javitch & Lei Shi & Harel Weinstein, 2011. "The Substrate-Driven Transition to an Inward-Facing Conformation in the Functional Mechanism of the Dopamine Transporter," PLOS ONE, Public Library of Science, vol. 6(1), pages 1-15, January.
    7. Joanne L. Parker & Justin C. Deme & Dimitrios Kolokouris & Gabriel Kuteyi & Philip C. Biggin & Susan M. Lea & Simon Newstead, 2021. "Molecular basis for redox control by the human cystine/glutamate antiporter system xc−," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    8. Heidi Koldsø & Pernille Noer & Julie Grouleff & Henriette Elisabeth Autzen & Steffen Sinning & Birgit Schiøtt, 2011. "Unbiased Simulations Reveal the Inward-Facing Conformation of the Human Serotonin Transporter and Na+ Ion Release," PLOS Computational Biology, Public Library of Science, vol. 7(10), pages 1-14, October.
    9. Patrick Roth & Jean-Marc Jeckelmann & Inken Fender & Zöhre Ucurum & Thomas Lemmin & Dimitrios Fotiadis, 2024. "Structure and mechanism of a phosphotransferase system glucose transporter," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    10. Yaning Li & Yingying Guo & Angelika Bröer & Lu Dai & Stefan Brӧer & Renhong Yan, 2024. "Cryo-EM structure of the human Asc-1 transporter complex," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    11. Yongchan Lee & Pattama Wiriyasermkul & Pornparn Kongpracha & Satomi Moriyama & Deryck J. Mills & Werner Kühlbrandt & Shushi Nagamori, 2022. "Ca2+-mediated higher-order assembly of heterodimers in amino acid transport system b0,+ biogenesis and cystinuria," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0160219. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.