Subunit Arrangement and Function in NMDA Receptors

Journal Article · Sat Jan 01 04:00:00 EST 2005 · Nature

DOI:https://doi.org/10.1038/nature04089· OSTI ID:913700

Furukawa, H; Singh, S; Mancusso, R; Gouaux, E

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 913700
• Report Number(s): BNL--78268-2007-JA
• Journal Information: Nature, Journal Name: Nature Vol. 438; ISSN NATUAS; ISSN 0028-0836
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CATIONS
CENTRAL NERVOUS SYSTEM
CRYSTAL STRUCTURE
DEACTIVATION
FUNCTIONALS
GLYCINE
LEARNING
LIGANDS
OPENINGS
PHYSIOLOGY
TYROSINE
national synchrotron light source