+Open data
-Basic information
Entry | Database: PDB / ID: 8uue | |||||||||||||||
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Title | Glycine-bound GluN1a-3A LBD heterotetramer (local refinement) | |||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Channel / receptor | |||||||||||||||
Function / homology | Function and homology information negative regulation of dendritic spine development / excitatory chemical synaptic transmission / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / glutamate receptor activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins ...negative regulation of dendritic spine development / excitatory chemical synaptic transmission / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / glutamate receptor activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / glycine binding / positive regulation of calcium ion transport into cytosol / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / dendrite development / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / monoatomic cation transport / positive regulation of excitatory postsynaptic potential / Long-term potentiation / ligand-gated monoatomic ion channel activity / excitatory synapse / positive regulation of synaptic transmission, glutamatergic / prepulse inhibition / calcium ion homeostasis / synaptic cleft / glutamate-gated calcium ion channel activity / EPHB-mediated forward signaling / presynaptic modulation of chemical synaptic transmission / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / regulation of membrane potential / excitatory postsynaptic potential / protein phosphatase 2A binding / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / postsynaptic density membrane / visual learning / modulation of chemical synaptic transmission / brain development / calcium channel activity / regulation of synaptic plasticity / terminal bouton / rhythmic process / calcium ion transport / synaptic vesicle / presynapse / signaling receptor activity / RAF/MAP kinase cascade / amyloid-beta binding / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / calmodulin binding / postsynaptic density / neuron projection / neuronal cell body / glutamatergic synapse / synapse / dendrite / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / identical protein binding / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.96 Å | |||||||||||||||
Authors | Michalski, K. / Furukawa, H. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Sci Adv / Year: 2024 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. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8uue.cif.gz | 216 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8uue.ent.gz | 168.9 KB | Display | PDB format |
PDBx/mmJSON format | 8uue.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8uue_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8uue_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8uue_validation.xml.gz | 47.7 KB | Display | |
Data in CIF | 8uue_validation.cif.gz | 69 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uu/8uue ftp://data.pdbj.org/pub/pdb/validation_reports/uu/8uue | HTTPS FTP |
-Related structure data
Related structure data | 42580MC 8uswC 8usxC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 45902.477 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRIN1, NMDAR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q05586 #2: Protein | Mass: 45535.320 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRIN3A, KIAA1973 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8TCU5 |
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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 |
-Sample preparation
Component | Name: Glycine-bound GluN1-3A LBD heterotetramer (local refinement) Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.4 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: OTHER / Nominal defocus max: 2200 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.96 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 225900 / Symmetry type: POINT |