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Open data
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Basic information
| Entry | Database: PDB / ID: 9pzx | |||||||||||||||||||||||||||
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| Title | GluN1/GluN2A in complex with 3D2 Fab, local ATD dimer | |||||||||||||||||||||||||||
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Keywords | TRANSPORT PROTEIN / ligand-gated ion channel / NMDA / antibody / complex | |||||||||||||||||||||||||||
| Function / homology | Function and homology informationregulation of response to alcohol / response to ammonium ion / neurotransmitter receptor transport, plasma membrane to endosome / receptor recycling / response to environmental enrichment / directional locomotion / EPHB-mediated forward signaling / pons maturation / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide ...regulation of response to alcohol / response to ammonium ion / neurotransmitter receptor transport, plasma membrane to endosome / receptor recycling / response to environmental enrichment / directional locomotion / EPHB-mediated forward signaling / pons maturation / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / regulation of cell communication / auditory behavior / positive regulation of Schwann cell migration / olfactory learning / conditioned taste aversion / response to other organism / cellular response to magnesium ion / dendritic branch / regulation of respiratory gaseous exchange / response to methylmercury / protein localization to postsynaptic membrane / serotonin metabolic process / regulation of ARF protein signal transduction / response to manganese ion / response to carbohydrate / transmitter-gated monoatomic ion channel activity / suckling behavior / positive regulation of inhibitory postsynaptic potential / sleep / cellular response to dsRNA / propylene metabolic process / response to glycine / regulation of NMDA receptor activity / cellular response to lipid / locomotion / dendritic spine organization / RAF/MAP kinase cascade / response to amine / Synaptic adhesion-like molecules / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / response to glycoside / NMDA selective glutamate receptor complex / voltage-gated monoatomic cation channel activity / glutamate binding / neurotransmitter receptor complex / ligand-gated sodium channel activity / glutamate receptor signaling pathway / regulation of axonogenesis / calcium ion transmembrane import into cytosol / neuromuscular process / response to morphine / regulation of dendrite morphogenesis / protein heterotetramerization / male mating behavior / regulation of synapse assembly / spinal cord development / glycine binding / startle response / cellular response to zinc ion / dopamine metabolic process / positive regulation of reactive oxygen species biosynthetic process / parallel fiber to Purkinje cell synapse / response to lithium ion / monoatomic cation transmembrane transport / monoatomic ion channel complex / cellular response to glycine / positive regulation of calcium ion transport into cytosol / regulation of postsynaptic membrane potential / response to light stimulus / action potential / modulation of excitatory postsynaptic potential / associative learning / positive regulation of dendritic spine maintenance / conditioned place preference / regulation of neuronal synaptic plasticity / social behavior / positive regulation of protein targeting to membrane / Unblocking of NMDA receptors, glutamate binding and activation / monoatomic cation transport / glutamate receptor binding / prepulse inhibition / long-term memory / neuron development / multicellular organismal response to stress / phosphatase binding / positive regulation of synaptic transmission, glutamatergic / postsynaptic density, intracellular component / response to fungicide / monoatomic cation channel activity / synaptic cleft / calcium ion homeostasis / glutamate-gated receptor activity / cellular response to manganese ion / glutamate-gated calcium ion channel activity / neurogenesis / presynaptic active zone membrane / cell adhesion molecule binding / dendrite membrane / excitatory synapse Similarity search - Function | |||||||||||||||||||||||||||
| Biological species | ![]() ![]() | |||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.76 Å | |||||||||||||||||||||||||||
Authors | Kim, J. / Gouaux, E. | |||||||||||||||||||||||||||
| Funding support | United States, 1items
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Citation | Journal: Sci Adv / Year: 2026Title: Cryo-EM of autoantibody-bound NMDA receptors reveals antigenic hotspots in an active immunization model of anti-NMDAR encephalitis. Authors: Junhoe Kim / Farzad Jalali-Yazdi / Brian E Jones / Gary L Westbrook / Eric Gouaux / ![]() Abstract: Autoantibodies targeting synaptic membrane proteins are associated with autoimmune encephalitis manifested by seizures, psychosis, and memory dysfunction. Anti--methyl-d-aspartate receptor (NMDAR) ...Autoantibodies targeting synaptic membrane proteins are associated with autoimmune encephalitis manifested by seizures, psychosis, and memory dysfunction. Anti--methyl-d-aspartate receptor (NMDAR) encephalitis, a prototype of these autoimmune synaptic disorders, is unexpectedly common. Unfortunately, how the native repertoire of anti-NMDAR autoantibodies recognizes NMDARs and the precise locations of antigenic epitopes remain poorly understood. Here, we used an active immunization model that closely mimics the human disease to immunize adult mice with intact GluN1/GluN2A receptors, resulting in fulminant autoimmune encephalitis. Serum was collected at 6 weeks postimmunization for single-particle cryo-electron microscopy of GluN1/GluN2A receptors complexed with purified polyclonal anti-NMDAR autoantibody fragments. Native autoantibodies recognized two distinct binding sites on the GluN1 amino-terminal domain, which we confirmed using monoclonal antibodies bound to native NMDARs purified from mouse brain. Structural analysis of autoantibody-bound NMDAR complexes identified antigenic hotspots within the GluN1 amino-terminal domain. These hotspots provide potential targets for therapeutic intervention. | |||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9pzx.cif.gz | 188.1 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9pzx.ent.gz | 129.2 KB | Display | PDB format |
| PDBx/mmJSON format | 9pzx.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pz/9pzx ftp://data.pdbj.org/pub/pdb/validation_reports/pz/9pzx | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 72085MC ![]() 9pzqC ![]() 9pzrC ![]() 9pzsC ![]() 9pztC ![]() 9pzuC ![]() 9pzvC ![]() 9pzwC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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| 1 |
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Components
-Glutamate receptor ionotropic, NMDA ... , 2 types, 2 molecules AB
| #1: Protein | Mass: 95372.164 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human) / References: UniProt: P35439 |
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| #2: Protein | Mass: 97163.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human) / References: UniProt: Q00959 |
-Antibody , 2 types, 2 molecules JK
| #3: Antibody | Mass: 15448.522 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human) |
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| #4: Antibody | Mass: 13989.831 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human) |
-Sugars , 2 types, 5 molecules 
| #5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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| #6: Sugar | ChemComp-NAG / |
-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-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: GluN1/GluN2A in complex with 3D2 Fab, local ATD dimer / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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| Molecular weight | Value: 0.110 MDa / Experimental value: NO |
| Source (natural) | Organism: ![]() |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 8 |
| Specimen | Conc.: 0.05 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 290 K |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm |
| Specimen holder | Cryogen: NITROGEN |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of real images: 6721 |
| EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
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Processing
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| CTF correction | Type: NONE | ||||||||||||||||||||||||
| Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.76 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 366876 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Highest resolution: 2.76 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) |
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United States, 1items
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PDBj






Homo sapiens (human)
FIELD EMISSION GUN