View source for 5fxh


==GluN1b-GluN2B NMDA receptor in non-active-1 conformation==
<StructureSection load='5fxh' size='340' side='right' caption='[[5fxh]], [[Resolution|resolution]] 6.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fxh]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FXH FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fxg|5fxg]], [[5fxi|5fxi]], [[5fxj|5fxj]], [[5fxk|5fxk]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fxh OCA], [http://pdbe.org/5fxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fxh RCSB], [http://www.ebi.ac.uk/pdbsum/5fxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fxh ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/NMDZ1_RAT NMDZ1_RAT]] NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. Plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors.<ref>PMID:15996549</ref>  [[http://www.uniprot.org/uniprot/NMDE2_RAT NMDE2_RAT]] NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity). 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The physiology of N-methyl-d-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed mainly of GluN1 and GluN2 subunits. Activation of NMDA receptors requires binding of neurotransmitter agonists to a ligand-binding domain (LBD) and structural rearrangement of an amino-terminal domain (ATD). Recent crystal structures of GluN1-GluN2B NMDA receptors bound to agonists and an allosteric inhibitor, ifenprodil, represent the allosterically inhibited state. However, how the ATD and LBD move to activate the NMDA receptor ion channel remains unclear. Here we applied X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology to rat NMDA receptors to show that, in the absence of ifenprodil, the bi-lobed structure of GluN2 ATD adopts an open conformation accompanied by rearrangement of the GluN1-GluN2 ATD heterodimeric interface, altering subunit orientation in the ATD and LBD and forming an active receptor conformation that gates the ion channel.

Activation of NMDA receptors and the mechanism of inhibition by ifenprodil.,Tajima N, Karakas E, Grant T, Simorowski N, Diaz-Avalos R, Grigorieff N, Furukawa H Nature. 2016 May 2. doi: 10.1038/nature17679. PMID:27135925<ref>PMID:27135925</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5fxh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Diaz-Avalos, R]]
[[Category: Furukawa, H]]
[[Category: Grant, T]]
[[Category: Grigorieff, N]]
[[Category: Karakas, E]]
[[Category: Simorowski, N]]
[[Category: Tajima, N]]
[[Category: Glun1]]
[[Category: Glun2b]]
[[Category: Glutamate receptor]]
[[Category: Ion channel]]
[[Category: Nmda receptor]]
[[Category: Signaling protein]]
[[Category: Transport protein]]