+Open data
-Basic information
Entry | Database: PDB / ID: 8vuy | ||||||
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Title | Rat GluN1-2B with Fab 003-102 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / Channel / heterotetramer / receptor / antibody | ||||||
Function / homology | Function and homology information neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / regulation of postsynaptic cytosolic calcium ion concentration / cellular response to magnesium starvation / sensory organ development / sensitization / pons maturation / positive regulation of Schwann cell migration / regulation of cell communication ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / regulation of postsynaptic cytosolic calcium ion concentration / cellular response to magnesium starvation / sensory organ development / sensitization / pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / regulation of protein kinase A signaling / conditioned taste aversion / response to hydrogen sulfide / regulation of respiratory gaseous exchange / dendritic branch / positive regulation of inhibitory postsynaptic potential / apical dendrite / protein localization to postsynaptic membrane / regulation of ARF protein signal transduction / fear response / response to methylmercury / response to other organism / propylene metabolic process / response to glycine / positive regulation of cysteine-type endopeptidase activity / response to carbohydrate / negative regulation of dendritic spine maintenance / cellular response to dsRNA / interleukin-1 receptor binding / voltage-gated monoatomic cation channel activity / cellular response to lipid / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / response to growth hormone / positive regulation of glutamate secretion / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA selective glutamate receptor complex / response to manganese ion / parallel fiber to Purkinje cell synapse / response to morphine / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / protein heterotetramerization / regulation of synapse assembly / positive regulation of reactive oxygen species biosynthetic process / male mating behavior / regulation of axonogenesis / regulation of dendrite morphogenesis / glycine binding / positive regulation of calcium ion transport into cytosol / heterocyclic compound binding / receptor clustering / suckling behavior / response to amine / startle response / small molecule binding / monoatomic cation transmembrane transport / action potential / regulation of neuronal synaptic plasticity / associative learning / monoatomic cation transport / behavioral response to pain / regulation of MAPK cascade / social behavior / response to magnesium ion / ligand-gated monoatomic ion channel activity / extracellularly glutamate-gated ion channel activity / positive regulation of excitatory postsynaptic potential / cellular response to organic cyclic compound / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / behavioral fear response / cellular response to manganese ion / postsynaptic density, intracellular component / phosphatase binding / glutamate receptor binding / neuron development / multicellular organismal response to stress / long-term memory / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain / calcium ion homeostasis / monoatomic cation channel activity / D2 dopamine receptor binding / response to electrical stimulus / regulation of neuron apoptotic process / glutamate-gated receptor activity / synaptic cleft / response to fungicide / response to mechanical stimulus Similarity search - Function | ||||||
Biological species | Rattus norvegicus (Norway rat) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.81 Å | ||||||
Authors | Michalski, K. / Furukawa, H. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis. Authors: Kevin Michalski / Taha Abdulla / Sam Kleeman / Lars Schmidl / Ricardo Gómez / Noriko Simorowski / Francesca Vallese / Harald Prüss / Manfred Heckmann / Christian Geis / Hiro Furukawa / Abstract: Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-D-aspartate receptor (NMDAR) ...Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most dominant autoimmune encephalitis; however, insights into how autoantibodies recognize and alter receptor functions remain limited. Here we determined structures of human and rat NMDARs bound to three distinct patient-derived antibodies using single-particle electron cryo-microscopy. These antibodies bind different regions within the amino-terminal domain of the GluN1 subunit. Through electrophysiology, we show that all three autoantibodies acutely and directly reduced NMDAR channel functions in primary neurons. Antibodies show different stoichiometry of binding and antibody-receptor complex formation, which in one antibody, 003-102, also results in reduced synaptic localization of NMDARs. These studies demonstrate mechanisms of diverse epitope recognition and direct channel regulation of anti-NMDAR autoantibodies underlying autoimmune encephalitis. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8vuy.cif.gz | 624.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8vuy.ent.gz | 490.5 KB | Display | PDB format |
PDBx/mmJSON format | 8vuy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8vuy_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8vuy_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 8vuy_validation.xml.gz | 97 KB | Display | |
Data in CIF | 8vuy_validation.cif.gz | 148.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vu/8vuy ftp://data.pdbj.org/pub/pdb/validation_reports/vu/8vuy | HTTPS FTP |
-Related structure data
Related structure data | 43544MC 8vuhC 8vujC 8vulC 8vunC 8vuqC 8vurC 8vusC 8vutC 8vuuC 8vuvC 8vvhC 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: 91944.094 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin1, Nmdar1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P35439 #2: Protein | Mass: 91269.125 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin2b / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q00960 #3: Antibody | Mass: 12477.862 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Antibody | Mass: 11582.475 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) Has protein modification | 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 |
-Sample preparation
Component | Name: Rat GluN1-2B with Fab 003-102 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | 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 / Cs: 2.7 mm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software | Name: cryoSPARC / Category: 3D reconstruction | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 516895 / Symmetry type: POINT | ||||||||||||||||||||||||
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