8e93

From Proteopedia

(Difference between revisions)

Revision as of 08:21, 7 December 2022

D-cycloserine and glutamate bound Human GluN1a-GluN2C NMDA receptor in splayed conformation

Structural highlights

8e93 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.
Ligands:	,
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

Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders.

Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs.,Chou TH, Kang H, Simorowski N, Traynelis SF, Furukawa H Mol Cell. 2022 Dec 1;82(23):4548-4563.e4. doi: 10.1016/j.molcel.2022.10.008. Epub , 2022 Oct 28. PMID:36309015^[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
↑ Chou TH, Kang H, Simorowski N, Traynelis SF, Furukawa H. Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. Mol Cell. 2022 Dec 1;82(23):4548-4563.e4. doi: 10.1016/j.molcel.2022.10.008. Epub , 2022 Oct 28. PMID:36309015 doi:http://dx.doi.org/10.1016/j.molcel.2022.10.008

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8e93"

Categories: Homo sapiens | Large Structures | Chou T-H | Furukawa H

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8e93 is ON HOLD
+==D-cycloserine and glutamate bound Human GluN1a-GluN2C NMDA receptor in splayed conformation==
+<StructureSection load='8e93' size='340' side='right'caption='[[8e93]], [[Resolution|resolution]] 3.71&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8e93]] 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=8E93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E93 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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=8e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e93 OCA], [https://pdbe.org/8e93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e93 RCSB], [https://www.ebi.ac.uk/pdbsum/8e93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e93 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 ==
+Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders.
-Authors:
+Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs.,Chou TH, Kang H, Simorowski N, Traynelis SF, Furukawa H Mol Cell. 2022 Dec 1;82(23):4548-4563.e4. doi: 10.1016/j.molcel.2022.10.008. Epub , 2022 Oct 28. PMID:36309015<ref>PMID:36309015</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8e93" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chou T-H]]
+[[Category: Furukawa H]]

8e93

From Proteopedia

Revision as of 08:21, 7 December 2022

D-cycloserine and glutamate bound Human GluN1a-GluN2C NMDA receptor in splayed conformation

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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