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