Referenced in: none

Automatically associated channels: Slo1

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

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

Journal, date & volume: Nat Commun, 2011 , 2, 294

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21522138

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.