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Yorodumi- PDB-6wi1: GluN1b-GluN2B NMDA receptor in active conformation stabilized by ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6wi1 | |||||||||
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Title | GluN1b-GluN2B NMDA receptor in active conformation stabilized by inter-GluN1b-GluN2B subunit cross-linking | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / NMDARs / Ligand-gated ion channels / METAL TRANSPORT / Ionotropic glutamate receptor | |||||||||
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 / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / response to other organism / 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 / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / cellular response to dsRNA / response to morphine / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / positive regulation of glutamate secretion / response to growth hormone / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA selective glutamate receptor complex / glutamate-gated calcium ion channel activity / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor signaling pathway / response to manganese ion / calcium ion transmembrane import into cytosol / 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 / regulation of dendrite morphogenesis / male mating behavior / regulation of axonogenesis / heterocyclic compound binding / suckling behavior / startle response / behavioral response to pain / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / response to amine / receptor clustering / regulation of MAPK cascade / social behavior / associative learning / response to magnesium ion / positive regulation of excitatory postsynaptic potential / monoatomic cation transport / ligand-gated monoatomic ion channel activity / excitatory synapse / cellular response to organic cyclic compound / extracellularly glutamate-gated ion channel activity / cellular response to glycine / small molecule binding / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / neuron development / regulation of postsynaptic membrane potential / behavioral fear response / phosphatase binding / glutamate receptor binding / postsynaptic density, intracellular component / calcium ion homeostasis / cellular response to manganese ion / D2 dopamine receptor binding / prepulse inhibition / multicellular organismal response to stress / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / monoatomic cation channel activity / regulation of neuron apoptotic process / response to electrical stimulus / presynaptic active zone membrane / synaptic cleft / glutamate-gated receptor activity Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.62 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 | 6wi1.cif.gz | 547.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6wi1.ent.gz | 446.9 KB | Display | PDB format |
PDBx/mmJSON format | 6wi1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wi/6wi1 ftp://data.pdbj.org/pub/pdb/validation_reports/wi/6wi1 | HTTPS FTP |
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-Related structure data
Related structure data | 21682MC 6usuC 6usvC 6whrC 6whsC 6whtC 6whuC 6whvC 6whwC 6whxC 6whyC 6wi0C 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: 97741.727 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P35439*PLUS #2: Protein | Mass: 98878.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q00960*PLUS #3: 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 #4: Sugar | ChemComp-NAG / Has ligand of interest | N | |
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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: 3.62 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 155641 / Symmetry type: POINT |