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Gating the channel pore of ionotropic glutamate receptors with bacterial substrate binding proteins

View ORCID ProfileMax Bernhard, View ORCID ProfileBodo Laube
doi: https://doi.org/10.1101/2021.01.27.428399
Max Bernhard
1Department of Biology, Neurophysiology and Neurosensory Systems, Technical University of Darmstadt, Schnittspahnstrasse 3, 64287 Darmstadt, Germany
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Bodo Laube
1Department of Biology, Neurophysiology and Neurosensory Systems, Technical University of Darmstadt, Schnittspahnstrasse 3, 64287 Darmstadt, Germany
2Centre for Synthetic Biology, Technical University of Darmstadt, 64283 Darmstadt, Germany
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  • For correspondence: laube@bio.tu-darmstadt.de
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Abstract

Tetrameric ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission in the mammalian central nervous system and are involved in learning, memory formation, and pathological processes. Based on structural and sequence similarities of the ligand-binding and channel domains of iGluR subunits to bacterial binding proteins and potassium channels, iGluRs are thought to have originally arisen from their fusion. Here we report the functional coupling of the bacterial ectoine binding protein EhuB to the channel pore-forming transmembrane domains of the bacterial GluR0 receptor by stabilization of dimeric binding domains. Insertion of a disulfide bridge in the dimer interface abolished desensitization of the channel current analogous to mammalian iGluRs. These results demonstrate the functional compatibility of bacterial binding proteins to the gate of the channel pore of an iGluR. Moreover, our results highlight the modular structure and crucial role of binding domain dimerization in the functional evolution of iGluRs.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Competing interests: The authors declare no competing interests.

  • Data availability: All data supporting the findings of this study are available within the article or are available from the corresponding author upon reasonable request. All cDNA constructs are available from the corresponding author based on reasonable request.

  • Ethical approval: All procedures involving animals were in accordance with the guidelines and regulations of the local animal care and use committee. Methods were approved by the Technical University of Darmstadt (II25.3-19c20/15, RP Darmstadt, Germany).

  • Abbreviations

    AMPA
    α-amino-3-hydroxy-5-methyl-4-isoaxazolepropionic acid
    CTD
    C-terminal domain
    iGluR
    ionotropic glutamate receptor
    LBD
    ligand binding domain
    NTD
    N-terminal domain
    RMSD
    root-mean-square deviation
    SBD
    substrate binding domain
    SBP
    substrate binding protein
    TMD
    transmembrane domain
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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    Posted January 27, 2021.
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    Gating the channel pore of ionotropic glutamate receptors with bacterial substrate binding proteins
    Max Bernhard, Bodo Laube
    bioRxiv 2021.01.27.428399; doi: https://doi.org/10.1101/2021.01.27.428399
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    Gating the channel pore of ionotropic glutamate receptors with bacterial substrate binding proteins
    Max Bernhard, Bodo Laube
    bioRxiv 2021.01.27.428399; doi: https://doi.org/10.1101/2021.01.27.428399

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