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

Vance, K. M., Simorowski, N., Traynelis, S. F., Furukawa, H. (2011) Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. Nature Communications, 2. ISSN 2041-1723

URL: http://www.ncbi.nlm.nih.gov/pubmed/21522138
DOI: 10.1038/ncomms1295

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.

Item Type: Paper
Additional Information:
Uncontrolled Keywords: d-aspartate receptors glutamate receptors crystal structures homocysteic acid binding core synaptic currents false transmitter channel kinetics central neurons partial agonism
Subjects: bioinformatics > genomics and proteomics > small molecules > NMDA receptor
CSHL Authors:
Communities: CSHL labs > Furukawa lab
Depositing User: Leigh Johnson
Date Deposited: 06 Mar 2012 19:02
Last Modified: 08 Sep 2017 15:36
PMCID: PMC3302728
Related URLs:
Dataset ID:
URI: http://repository.cshl.edu/id/eprint/25156

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