2A5S

Crystal Structure Of The NR2A Ligand Binding Core In Complex With Glutamate

Summary for 2A5S

• Entry DOI: 10.2210/pdb2a5s/pdb
• Related: 1PB7 2A5T
• Descriptor: N-methyl-D-aspartate receptor NMDAR2A subunit, GLUTAMIC ACID (3 entities in total)
• Functional Keywords: protein-ligand complex, metal transport, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 1
• Total formula weight: 31999.52

Authors

Furukawa, H.,Singh, S.K.,Mancusso, R.,Gouaux, E. (deposition date: 2005-06-30, release date: 2005-11-15, Last modification date: 2024-10-30)

Primary citation

Furukawa, H.,Singh, S.K.,Mancusso, R.,Gouaux, E.
Subunit arrangement and function in NMDA receptors
Nature, 438:185-192, 2005

PubMed 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.

PubMed: 16281028
DOI: 10.1038/nature04089

Experimental method

X-RAY DIFFRACTION (1.7 Å)