PDBsum entry 2ipv

Membrane protein

PDB id: 2ipv

Contents

Protein chain

256 a.a.

Ligands

GLU

Theoretical model

PDB id:

2ipv

Name:

Membrane protein

Title:

Homology model of nr2b subunit of nmda receptor in complex with glutamate

Structure:

Glutamate binding site of nr2b subunit of nmda receptor. Chain: x

Source:

Homo sapiens. Human

Authors:

P.A.Abreu,M.G.Albuquerque,C.R.Rodrigues,R.Paes-De-Carvalho, S.Pinheiro,H.C.Castro

Key ref:

H.Furukawa et al. (2005). Subunit arrangement and function in NMDA receptors. Nature, 438, 185-192. PubMed id: 16281028 DOI: 10.1038/nature04089

Date:

12-Oct-06 Release date: 24-Oct-06

Protein chain

No UniProt id for this chain

Struc: 256 a.a.

DOI no: 10.1038/nature04089

Nature 438:185-192 (2005)

PubMed id: 16281028

Subunit arrangement and function in NMDA receptors.

H.Furukawa, S.K.Singh, R.Mancusso, E.Gouaux.

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.

Selected figure(s)

Figure 2.
Figure 2: Structure of NR1-NR2A S1S2. a, Side view of the NR1-NR2A S1S2 heterodimer in complex with glycine and glutamate. NR1 and NR2A are coloured green and blue, respectively. Glycine, glutamate and the C atom of the glycine residue in the Gly-Thr dipeptide linker are shown as spheres. The arrow indicates the pseudo two-fold axis between the protomers. b, View of the structure from the 'top'. The interface between NR1 and NR2A is sliced into three sections denoted sites I-III. c-e, Magnified view of the interactions at sites I, II and III. Dashed lines indicate hydrogen bonds or salt bridges. The interacting residues from NR1 and NR2A are coloured white and orange, respectively. f, g, Structural comparison between the NR1-NR2A (green-blue) S1S2 heterodimer and the glutamate-bound GluR2 S1S2 (pink) homodimer (PDB code 1FTJ). Superimposed structures are viewed from the side and 'top' of the molecules in f and g, respectively. Superposition was carried out on 256 residues from domain 1 with the program LSQKAB^50. The C atoms of the glycine residues in the Gly-Thr dipeptide linkers are shown as spheres.

Figure 5.
Figure 5: Superposition of NR1-NR2A S1S2 and the GluR2 S1S2-aniracetam complex. a, Overlay of the GluR2 S1S2 dimer bound to glutamate and aniracetam (Ani, pink) onto the NR1-NR2A S1S2 dimer (green and blue) viewed from the same angle as in Fig. 1b. b, Magnification of the NR1 Y535 site and the aniracetam-binding site viewed from the same angle as in a. Two water molecules, W1 and W2 (cyan spheres), participate in stabilizing the NR1-NR2A interaction. c, Side view of the NR1 Y535 site. Note that the position of the aniracetam molecule (pink) overlaps with that of the aromatic side chain of NR1 Y535.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2005, 438, 185-192) copyright 2005.

Figures were selected by an automated process.