Subunit arrangement and function in NMDA receptors

Furukawa, H., Singh, S. K., Mancusso, R., Gouaux, E. (November 2005) Subunit arrangement and function in NMDA receptors. Nature, 438 (7065). pp. 185-192. ISSN 0028-08361476-4687 (Electronic)1476-4687 (Linking) (Public Dataset)

DOI: 10.1038/nature04089


Excitatory neurotransmission mediated by NMDA (N-methyl-d-aspartate) receptors is fundamental to the physiology of the mammalian central nervous system. These receptors are heteromeric ion channels that for activation require binding of glycine and glutamate to the NR1 and NR2 subunits, respectively. NMDA receptor function is characterized by slow channel opening and deactivation, and the resulting influx of cations initiates signal transduction cascades that are crucial to higher functions including learning and memory. Here we report crystal structures of the ligand-binding core of NR2A with glutamate and that of the NR1–NR2A heterodimer with glutamate and glycine. The NR2A–glutamate complex defines the determinants of glutamate and NMDA recognition, and the NR1–NR2A heterodimer suggests a mechanism for ligand-induced ion channel opening. Analysis of the heterodimer interface, together with biochemical and electrophysiological experiments, confirms that the NR1–NR2A heterodimer is the functional unit in tetrameric NMDA receptors and that tyrosine 535 of NR1, located in the subunit interface, modulates the rate of ion channel deactivation.

Item Type: Paper
Uncontrolled Keywords: Animals Binding Sites Dimerization Disulfides chemistry metabolism Electrophysiology Glutamic Acid metabolism Ion Channel Gating Ligands Models Molecular Oocytes Protein Structure Quaternary Protein Subunits chemistry genetics metabolism Rats Receptors N-Methyl-D-Aspartate chemistry genetics metabolism Substrate Specificity
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > NMDA receptor
CSHL Authors:
Communities: CSHL labs > Furukawa lab
Depositing User: Leigh Johnson
Date: 10 November 2005
Date Deposited: 06 Mar 2012 19:20
Last Modified: 08 Sep 2017 16:26
Related URLs:
Dataset ID:

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving