View source for 6irf


==Structure of the human GluN1/GluN2A NMDA receptor in the glutamate/glycine-bound state at pH 6.3, Class I==
<SX load='6irf' size='340' side='right' viewer='molstar' caption='[[6irf]], [[Resolution|resolution]] 5.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6irf]] 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=6IRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IRF 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]] 5.1&#8491;</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=6irf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6irf OCA], [https://pdbe.org/6irf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6irf RCSB], [https://www.ebi.ac.uk/pdbsum/6irf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6irf ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
N-methyl-D-aspartate (NMDA) receptors are critical for synaptic development and plasticity. While glutamate is the primary agonist, protons can modulate NMDA receptor activity at synapses during vesicle exocytosis by mechanisms that are unknown. We used cryo-electron microscopy to solve the structures of the human GluN1-GluN2A NMDA receptor at pH 7.8 and pH 6.3. Our structures demonstrate that the proton sensor predominantly resides in the N-terminal domain (NTD) of the GluN2A subunit and reveal the allosteric coupling mechanism between the proton sensor and the channel gate. Under high-pH conditions, the GluN2A-NTD adopts an "open-and-twisted" conformation. However, upon protonation at the lower pH, the GluN2A-NTD transits from an open- to closed-cleft conformation, causing rearrangements between the tetrameric NTDs and agonist-binding domains. The conformational mobility observed in our structures (presumably from protonation) is supported by molecular dynamics simulation. Our findings reveal the structural mechanisms by which protons allosterically inhibit human GluN1-GluN2A receptor activity.

Structural Basis of the Proton Sensitivity of Human GluN1-GluN2A NMDA Receptors.,Zhang JB, Chang S, Xu P, Miao M, Wu H, Zhang Y, Zhang T, Wang H, Zhang J, Xie C, Song N, Luo C, Zhang X, Zhu S Cell Rep. 2018 Dec 26;25(13):3582-3590.e4. doi: 10.1016/j.celrep.2018.11.071. PMID:30590034<ref>PMID:30590034</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6irf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
== References ==
<references/>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chang S]]
[[Category: Zhang J]]
[[Category: Zhang X]]
[[Category: Zhu S]]