View source for 7yfl


==Structure of GluN1a-GluN2D NMDA receptor in complex with agonists glycine and glutamate.==
<StructureSection load='7yfl' size='340' side='right'caption='[[7yfl]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7yfl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YFL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7yfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yfl OCA], [https://pdbe.org/7yfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yfl RCSB], [https://www.ebi.ac.uk/pdbsum/7yfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yfl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NMDE4_HUMAN NMDE4_HUMAN] Non-specific early-onset epileptic encephalopathy. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/NMDE4_HUMAN NMDE4_HUMAN] Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:9489750, PubMed:27616483, PubMed:26875626, PubMed:28126851). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:9489750).<ref>PMID:26875626</ref> <ref>PMID:27616483</ref> <ref>PMID:28095420</ref> <ref>PMID:28126851</ref> <ref>PMID:9489750</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
N-methyl-D-aspartate (NMDA) receptors are heterotetramers comprising two GluN1 and two alternate GluN2 (N2A-N2D) subunits. Here we report full-length cryo-EM structures of the human N1-N2D di-heterotetramer (di-receptor), rat N1-N2C di-receptor and N1-N2A-N2C tri-heterotetramer (tri-receptor) at a best resolution of 3.0 A. The bilobate N-terminal domain (NTD) in N2D intrinsically adopts a closed conformation, leading to a compact NTD tetramer in the N1-N2D receptor. Additionally, crosslinking the ligand-binding domain (LBD) of two N1 protomers significantly elevated the channel open probability (Po) in N1-N2D di-receptors. Surprisingly, the N1-N2C di-receptor adopted both symmetric (minor) and asymmetric (major) conformations, the latter further locked by an allosteric potentiator, PYD-106, binding to a pocket between the NTD and LBD in only one N2C protomer. Finally, the N2A and N2C subunits in the N1-N2A-N2C tri-receptor display a conformation close to one protomer in the N1-N2A and N1-N2C di-receptors, respectively. These findings provide a comprehensive structural understanding of diverse function in major NMDA receptor subtypes.

Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits.,Zhang J, Zhang M, Wang Q, Wen H, Liu Z, Wang F, Wang Y, Yao F, Song N, Kou Z, Li Y, Guo F, Zhu S Nat Struct Mol Biol. 2023 Mar 23. doi: 10.1038/s41594-023-00959-z. PMID:36959261<ref>PMID:36959261</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7yfl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Zhang JL]]
[[Category: Zhang M]]
[[Category: Zhu SJ]]