7yff
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7yff]] 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=7YFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YFF FirstGlance]. <br> | <table><tr><td colspan='2'>[[7yff]] 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=7YFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YFF FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7RC:( | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7RC:(2~{R})-4-(3-phosphonopropyl)piperazine-2-carboxylic+acid'>7RC</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=7yff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yff OCA], [https://pdbe.org/7yff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yff RCSB], [https://www.ebi.ac.uk/pdbsum/7yff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yff ProSAT]</span></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=7yff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yff OCA], [https://pdbe.org/7yff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yff RCSB], [https://www.ebi.ac.uk/pdbsum/7yff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yff ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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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. | 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 | + | 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 May;30(5):629-639. doi: 10.1038/s41594-023-00959-z. , Epub 2023 Mar 23. PMID:36959261<ref>PMID:36959261</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7yff" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7yff" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Structure of GluN1a-GluN2D NMDA receptor in complex with agonist glycine and competitive antagonist CPP.
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