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Yorodumi- PDB-6whu: GluN1b-GluN2B NMDA receptor in complex with SDZ 220-040 and L689,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6whu | |||||||||
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Title | GluN1b-GluN2B NMDA receptor in complex with SDZ 220-040 and L689,560, class 1 | |||||||||
Components | (Glutamate receptor ionotropic, NMDA ...) x 2 | |||||||||
Keywords | MEMBRANE PROTEIN / NMDARs / Ligand-gated ion channels / METAL TRANSPORT / Ionotropic glutamate receptor / GluN1 antagonist / GluN2B antagonist | |||||||||
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 / response to carbohydrate / regulation of monoatomic cation transmembrane transport / 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 / receptor clustering / suckling behavior / 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 / response to magnesium ion / positive regulation of excitatory postsynaptic potential / 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 / neuron development / positive regulation of dendritic spine maintenance / glutamate receptor binding / regulation of postsynaptic membrane potential / behavioral fear response / multicellular organismal response to stress / phosphatase binding / calcium ion homeostasis / D2 dopamine receptor binding / cellular response to manganese ion / prepulse inhibition / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / positive regulation of synaptic transmission / regulation of neuron apoptotic process / response to electrical stimulus / response to mechanical stimulus / glutamate-gated receptor activity / synaptic cleft / presynaptic active zone membrane / response to fungicide / cellular response to forskolin / monoatomic cation channel activity / sensory perception of pain Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.93 Å | |||||||||
Authors | Chou, T. / Tajima, N. / Furukawa, H. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell / Year: 2020 Title: Structural Basis of Functional Transitions in Mammalian NMDA Receptors. Authors: Tsung-Han Chou / Nami Tajima / Annabel Romero-Hernandez / Hiro Furukawa / Abstract: Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of ...Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology. | |||||||||
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 | 6whu.cif.gz | 531.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6whu.ent.gz | 415.2 KB | Display | PDB format |
PDBx/mmJSON format | 6whu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wh/6whu ftp://data.pdbj.org/pub/pdb/validation_reports/wh/6whu | HTTPS FTP |
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-Related structure data
Related structure data | 21676MC 6usuC 6usvC 6whrC 6whsC 6whtC 6whvC 6whwC 6whxC 6whyC 6wi0C 6wi1C 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
-Glutamate receptor ionotropic, NMDA ... , 2 types, 4 molecules ACBD
#1: Protein | Mass: 108085.633 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: 98845.859 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 |
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-Sugars , 2 types, 10 molecules
#3: Polysaccharide | Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / |
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-Non-polymers , 2 types, 4 molecules
#4: Chemical | #6: Chemical | |
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-Details
Has ligand of interest | 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: NMDA receptor GluN1b/2B functional ion channel complex Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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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 | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 85 % / Chamber temperature: 295 K |
-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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 64.5 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software | Name: cisTEM / Version: 1.0.0 / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Symmetry | Point symmetry: C2 (2 fold cyclic) |
3D reconstruction | Resolution: 3.93 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 159738 / Symmetry type: POINT |