Subunit arrangement and function in NMDA receptors

Hiroyasu Furukawa, Satinder K. Singh, Romina Mancusso, Eric Gouaux

Research output: Contribution to journalArticle

490 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalNature
Volume438
Issue number7065
DOIs
StatePublished - Nov 10 2005

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Glutamic Acid
Ion Channels
Glycine
Ligands
Aspartic Acid
Synaptic Transmission
Tyrosine
Cations
Signal Transduction
Central Nervous System
aspartic acid receptor
Learning

ASJC Scopus subject areas

  • General

Cite this

Furukawa, H., Singh, S. K., Mancusso, R., & Gouaux, E. (2005). Subunit arrangement and function in NMDA receptors. Nature, 438(7065), 185-192. https://doi.org/10.1038/nature04089

Subunit arrangement and function in NMDA receptors. / Furukawa, Hiroyasu; Singh, Satinder K.; Mancusso, Romina; Gouaux, Eric.

In: Nature, Vol. 438, No. 7065, 10.11.2005, p. 185-192.

Research output: Contribution to journalArticle

Furukawa, H, Singh, SK, Mancusso, R & Gouaux, E 2005, 'Subunit arrangement and function in NMDA receptors', Nature, vol. 438, no. 7065, pp. 185-192. https://doi.org/10.1038/nature04089
Furukawa H, Singh SK, Mancusso R, Gouaux E. Subunit arrangement and function in NMDA receptors. Nature. 2005 Nov 10;438(7065):185-192. https://doi.org/10.1038/nature04089
Furukawa, Hiroyasu ; Singh, Satinder K. ; Mancusso, Romina ; Gouaux, Eric. / Subunit arrangement and function in NMDA receptors. In: Nature. 2005 ; Vol. 438, No. 7065. pp. 185-192.
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