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Open data
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Basic information
Entry | Database: PDB / ID: 8usw | |||||||||||||||
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Title | CNQX-bound GluN1a-3A NMDA receptor | |||||||||||||||
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![]() | MEMBRANE PROTEIN / Channel / receptor | |||||||||||||||
Function / homology | ![]() negative regulation of dendritic spine development / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange ...negative regulation of dendritic spine development / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / glutamate receptor activity / response to morphine / NMDA glutamate receptor activity / Assembly and cell surface presentation of NMDA receptors / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / glutamate-gated calcium ion channel activity / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / calcium ion transmembrane import into cytosol / protein heterotetramerization / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / regulation of axonogenesis / male mating behavior / suckling behavior / startle response / dendrite development / response to amine / monoatomic cation transmembrane transport / monoatomic cation transport / regulation of neuronal synaptic plasticity / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / ligand-gated monoatomic ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / cellular response to manganese ion / calcium ion homeostasis / glutamate receptor binding / prepulse inhibition / monoatomic cation channel activity / long-term memory / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / sensory perception of pain / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / presynaptic modulation of chemical synaptic transmission / ionotropic glutamate receptor signaling pathway / excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / protein phosphatase 2A binding / learning / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / regulation of membrane potential / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / calcium channel activity / visual learning / modulation of chemical synaptic transmission / regulation of synaptic plasticity / response to organic cyclic compound / terminal bouton / cerebral cortex development / memory / synaptic vesicle membrane / intracellular calcium ion homeostasis / response to calcium ion / neuron cellular homeostasis / calcium ion transport / rhythmic process / synaptic vesicle / presynapse / presynaptic membrane / signaling receptor activity / amyloid-beta binding / protein-containing complex assembly Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.23 Å | |||||||||||||||
![]() | Michalski, K. / Furukawa, H. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel. Authors: Kevin Michalski / Hiro Furukawa / ![]() Abstract: -methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. ...-methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. Uniquely, NMDARs composed of GluN1 and GluN3 are activated exclusively by glycine, the neurotransmitter conventionally mediating inhibitory signaling when it binds to pentameric glycine receptors. The GluN1-3 NMDARs are vital for regulating neuronal excitability, circuit function, and specific behaviors, yet our understanding of their functional mechanism at the molecular level has remained limited. Here, we present cryo-electron microscopy structures of GluN1-3A NMDARs bound to an antagonist, CNQX, and an agonist, glycine. The structures show a 1-3-1-3 subunit heterotetrameric arrangement and an unprecedented pattern of GluN3A subunit orientation shift between the glycine-bound and CNQX-bound structures. Site-directed disruption of the unique subunit interface in the glycine-bound structure mitigated desensitization. Our study provides a foundation for understanding the distinct structural dynamics of GluN3 that are linked to the unique function of GluN1-3 NMDARs. | |||||||||||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 464.1 KB | Display | ![]() |
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PDB format | ![]() | 342.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 82.8 KB | Display | |
Data in CIF | ![]() | 128.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 42520MC ![]() 8usxC ![]() 8uueC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 95041.672 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 104837.195 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Chemical | Mass: 232.152 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C9H4N4O4 / Feature type: SUBJECT OF INVESTIGATION Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: CNQX-bound GluN1-3A NMDA receptor / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Value: 0.4 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: OTHER / Nominal defocus max: 2200 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: cryoSPARC / Category: 3D reconstruction |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 4.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 264487 / Symmetry type: POINT |