Ligand-specific Deactivation Time Course of GluN1/GluN2D NMDA Receptors

Journal Article · Sat Dec 31 04:00:00 EST 2011 · Nature Communications

DOI:https://doi.org/10.1038/ncomms1295· OSTI ID:1042316

Vance, K; Simorowski, N; Traynelis, S; Furukawa, H

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.

• Research Organization: BROOKHAVEN NATIONAL LABORATORY (BNL)
• Sponsoring Organization: USDOE SC OFFICE OF SCIENCE (SC)
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1042316
• Report Number(s): BNL--97994-2012-JA
• Journal Information: Nature Communications, Journal Name: Nature Communications Vol. 2; ISSN 2041-1723
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
BIOLOGICAL PATHWAYS
CRYSTAL STRUCTURE
CRYSTALLOGRAPHY
DEACTIVATION
ELECTROPHYSIOLOGY
LIGANDS
NERVE CELLS
RECEPTORS
REMOVAL