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Yorodumi- PDB-7ter: Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 non-act... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7ter | |||||||||
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Title | Cryo-EM structure of GluN1b-2B NMDAR in complex with Fab5 non-active2 conformation | |||||||||
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 / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / 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 / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / dendritic branch / response to other organism / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / positive regulation of inhibitory postsynaptic potential / apical dendrite / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / fear response / response to methylmercury / positive regulation of cysteine-type endopeptidase activity / voltage-gated monoatomic cation channel activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / NMDA glutamate receptor activity / response to morphine / positive regulation of glutamate secretion / response to growth hormone / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / heterocyclic compound binding / suckling behavior / receptor clustering / startle response / behavioral response to pain / response to amine / small molecule binding / regulation of neuronal synaptic plasticity / action potential / monoatomic cation transmembrane transport / monoatomic cation transport / associative learning / positive regulation of excitatory postsynaptic potential / regulation of MAPK cascade / response to magnesium ion / social behavior / ligand-gated monoatomic ion channel activity / cellular response to organic cyclic compound / excitatory synapse / extracellularly glutamate-gated ion channel activity / cellular response to glycine / positive regulation of dendritic spine maintenance / behavioral fear response / neuron development / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / postsynaptic density, intracellular component / cellular response to manganese ion / glutamate receptor binding / D2 dopamine receptor binding / multicellular organismal response to stress / long-term memory / positive regulation of synaptic transmission, glutamatergic / prepulse inhibition / monoatomic cation channel activity / detection of mechanical stimulus involved in sensory perception of pain / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / response to electrical stimulus / response to mechanical stimulus / glutamate-gated receptor activity Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.23 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 | 7ter.cif.gz | 693.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ter.ent.gz | 579.5 KB | Display | PDB format |
PDBx/mmJSON format | 7ter.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ter_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7ter_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7ter_validation.xml.gz | 112.6 KB | Display | |
Data in CIF | 7ter_validation.cif.gz | 169.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/te/7ter ftp://data.pdbj.org/pub/pdb/validation_reports/te/7ter | HTTPS FTP |
-Related structure data
Related structure data | 25850MC 7te4C 7te6C 7te9C 7tebC 7teeC 7teqC 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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-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: Antibody | Mass: 23844.684 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) #4: Antibody | Mass: 23855.256 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 complexed to Fab5 / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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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: 3000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 60 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: 5.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 39661 / Symmetry type: POINT |