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Yorodumi- PDB-7teb: Cryo-EM structure of GluN1b-2B NMDAR complexed to Fab2 non-active... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7teb | |||||||||
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Title | Cryo-EM structure of GluN1b-2B NMDAR complexed to Fab2 non-active1-like | |||||||||
Components |
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Keywords | SIGNALING PROTEIN/IMMUNE SYSTEM / Channel / antibody / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 / cellular response to magnesium starvation / NMDA selective glutamate receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / NMDA selective glutamate receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / protein localization to postsynaptic membrane / dendritic branch / regulation of respiratory gaseous exchange / propylene metabolic process / response to glycine / apical dendrite / response to other organism / fear response / response to methylmercury / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / response to morphine / glutamate-gated calcium ion channel activity / cellular response to dsRNA / regulation of monoatomic cation transmembrane transport / response to carbohydrate / negative regulation of dendritic spine maintenance / interleukin-1 receptor binding / cellular response to lipid / positive regulation of glutamate secretion / NMDA glutamate receptor activity / response to growth hormone / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / Synaptic adhesion-like molecules / parallel fiber to Purkinje cell synapse / calcium ion transmembrane import into cytosol / response to manganese ion / protein heterotetramerization / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / neuromuscular process / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / male mating behavior / regulation of dendrite morphogenesis / regulation of axonogenesis / heterocyclic compound binding / suckling behavior / receptor clustering / startle response / behavioral response to pain / regulation of neuronal synaptic plasticity / response to amine / monoatomic cation transmembrane transport / regulation of MAPK cascade / social behavior / small molecule binding / associative learning / positive regulation of excitatory postsynaptic potential / response to magnesium ion / monoatomic cation transport / ligand-gated monoatomic ion channel activity / excitatory synapse / extracellularly glutamate-gated ion channel activity / cellular response to organic cyclic compound / Unblocking of NMDA receptors, glutamate binding and activation / positive regulation of dendritic spine maintenance / neuron development / glutamate receptor binding / regulation of postsynaptic membrane potential / multicellular organismal response to stress / phosphatase binding / behavioral fear response / calcium ion homeostasis / cellular response to manganese ion / D2 dopamine receptor binding / prepulse inhibition / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / positive regulation of synaptic transmission / response to mechanical stimulus / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / presynaptic active zone membrane / glutamate-gated receptor activity / response to fungicide / cellular response to forskolin / monoatomic cation channel activity / sensory perception of pain Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.23 Å | |||||||||
Authors | Tajima, N. / Furukawa, H. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2022 Title: Development and characterization of functional antibodies targeting NMDA receptors. Authors: Nami Tajima / Noriko Simorowski / Remy A Yovanno / Michael C Regan / Kevin Michalski / Ricardo Gómez / Albert Y Lau / Hiro Furukawa / Abstract: N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct ...N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct activities has been considered an effective therapeutic strategy for neurological disorders and diseases. However, complete elimination of off-target effects of small chemical compounds has been challenging and thus, there is a need to explore alternative strategies for targeting NMDAR subtypes. Here we report identification of a functional antibody that specifically targets the GluN1-GluN2B NMDAR subtype and allosterically down-regulates ion channel activity as assessed by electrophysiology. Through biochemical analysis, x-ray crystallography, single-particle electron cryomicroscopy, and molecular dynamics simulations, we show that this inhibitory antibody recognizes the amino terminal domain of the GluN2B subunit and increases the population of the non-active conformational state. The current study demonstrates that antibodies may serve as specific reagents to regulate NMDAR functions for basic research and therapeutic objectives. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7teb.cif.gz | 630.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7teb.ent.gz | 520.8 KB | Display | PDB format |
PDBx/mmJSON format | 7teb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/te/7teb ftp://data.pdbj.org/pub/pdb/validation_reports/te/7teb | HTTPS FTP |
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-Related structure data
Related structure data | 25844MC 7te4C 7te6C 7te9C 7teeC 7teqC 7terC 7tesC 7tetC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 96944.891 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: 98797.820 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: Protein | Mass: 23914.781 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) #4: Antibody | Mass: 23572.031 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
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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: GluN1b-2B NMDAR - Fab2 / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Rattus norvegicus (Norway rat) |
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: 3500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 65 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING ONLY |
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3D reconstruction | Resolution: 4.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 30424 / Symmetry type: POINT |