6irg

From Proteopedia

(Difference between revisions)

Current revision

Structure of the human GluN1/GluN2A NMDA receptor in the glutamate/glycine-bound state at pH 6.3, Class II

6irg, resolution 5.50Å

Structural highlights

6irg is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 5.5Å
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NMDZ1_HUMAN Defects in GRIN1 are the cause of mental retardation autosomal dominant type 8 (MRD8) [MIM:614254. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.^[1]

Function

NMDZ1_HUMAN NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein 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 (By similarity).

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O, Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, D'Anjou G, Vanasse M, Srour M, Lafreniere RG, Drapeau P, Lacaille JC, Kim E, Lee JR, Igarashi K, Huganir RL, Rouleau GA, Michaud JL. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet. 2011 Mar 11;88(3):306-16. doi: 10.1016/j.ajhg.2011.02.001. Epub, 2011 Mar 3. PMID:21376300 doi:10.1016/j.ajhg.2011.02.001
↑ 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. Structural Basis of the Proton Sensitivity of Human GluN1-GluN2A NMDA Receptors. Cell Rep. 2018 Dec 26;25(13):3582-3590.e4. doi: 10.1016/j.celrep.2018.11.071. PMID:30590034 doi:http://dx.doi.org/10.1016/j.celrep.2018.11.071

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6irg"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6irg is ON HOLD  until Paper Publication
+==Structure of the human GluN1/GluN2A NMDA receptor in the glutamate/glycine-bound state at pH 6.3, Class II==
+<SX load='6irg' size='340' side='right' viewer='molstar' caption='[[6irg]], [[Resolution|resolution]] 5.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6irg]] 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=6IRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IRG 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]] 5.5&#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=6irg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6irg OCA], [https://pdbe.org/6irg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6irg RCSB], [https://www.ebi.ac.uk/pdbsum/6irg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6irg ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/NMDZ1_HUMAN NMDZ1_HUMAN] Defects in GRIN1 are the cause of mental retardation autosomal dominant type 8 (MRD8) [MIM:[https://omim.org/entry/614254 614254]. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.<ref>PMID:21376300</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/NMDZ1_HUMAN NMDZ1_HUMAN] NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein 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 (By similarity).
+<div style="background-color:#fffaf0;">
+== 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.
-Authors: Zhang, J., Chang, S., Zhang, X., Zhu, S.
+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>
-Description: Structure of the human GluN1/GluN2A NMDA receptor in the glutamate/glycine-bound state at pH 6.3, Class II
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chang, S]]
+<div class="pdbe-citations 6irg" style="background-color:#fffaf0;"></div>
-[[Category: Zhang, J]]
-[[Category: Zhu, S]]
+==See Also==
-[[Category: Zhang, X]]
+*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
+== References ==
+<references/>
+__TOC__
+</SX>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chang S]]
+[[Category: Zhang J]]
+[[Category: Zhang X]]
+[[Category: Zhu S]]

6irg

From Proteopedia

Current revision

Structure of the human GluN1/GluN2A NMDA receptor in the glutamate/glycine-bound state at pH 6.3, Class II

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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