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Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors

Author

Listed:
  • Katie M. Vance

    (Emory University School of Medicine, Rollins Research Center)

  • Noriko Simorowski

    (Cold Spring Harbor Laboratory, Keck Structural Biology Laboratory)

  • Stephen F. Traynelis

    (Emory University School of Medicine, Rollins Research Center)

  • Hiro Furukawa

    (Cold Spring Harbor Laboratory, Keck Structural Biology Laboratory)

Abstract

N-methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors that mediate a majority of excitatory synaptic transmission. One unique property of GluN1/GluN2D NMDA receptors is an unusually prolonged deactivation time course following the removal of L-glutamate. Here we show, using x-ray crystallography and electrophysiology, that the deactivation time course of GluN1/GluN2D receptors is influenced by the conformational variability of the ligand-binding domain (LBD) as well as the structure of the activating ligand. L-glutamate and L-CCG-IV induce significantly slower deactivation time courses compared with other agonists. Crystal structures of the isolated GluN2D LBD in complex with various ligands reveal that the binding of L-glutamate induces a unique conformation at the backside of the ligand-binding site in proximity to the region at which the transmembrane domain would be located in the intact receptors. These data suggest that the activity of the GluN1/GluN2D NMDA receptor is controlled distinctively by the endogenous neurotransmitter L-glutamate.

Suggested Citation

  • Katie M. Vance & Noriko Simorowski & Stephen F. Traynelis & Hiro Furukawa, 2011. "Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors," Nature Communications, Nature, vol. 2(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1295
    DOI: 10.1038/ncomms1295
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    Cited by:

    1. Nami Tajima & Noriko Simorowski & Remy A. Yovanno & Michael C. Regan & Kevin Michalski & Ricardo Gómez & Albert Y. Lau & Hiro Furukawa, 2022. "Development and characterization of functional antibodies targeting NMDA receptors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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