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

Authors: Vance, Katie M; Simorowski, Noriko; Traynelis, Stephen F; Furukawa, Hiro

Published In Nat Commun, (2011)

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.

PubMed ID: 21522138

MeSH Terms: Amino Acid Sequence; Animals; Crystallography, X-Ray; Glutamic Acid/chemistry*; Glutamic Acid/metabolism; HEK293 Cells; Humans; Kinetics; Ligands; Molecular Conformation; Molecular Sequence Data; Protein Conformation; Rats; Receptors, N-Methyl-D-Aspartate/chemistry*; Receptors, N-Methyl-D-Aspartate/genetics; Receptors, N-Methyl-D-Aspartate/metabolism; Recombinant Fusion Proteins/chemistry; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism