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Yorodumi- PDB-6usu: Crystal structure of GluN1/GluN2A ligand-binding domain in comple... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6usu | |||||||||
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Title | Crystal structure of GluN1/GluN2A ligand-binding domain in complex with L689,560 and glutamate | |||||||||
Components |
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Keywords | METAL TRANSPORT / NMDARs / LBD / Ion channels | |||||||||
Function / homology | Function and homology information neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / response to environmental enrichment / EPHB-mediated forward signaling ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / response to environmental enrichment / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / serotonin metabolic process / conditioned place preference / 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 / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / cellular response to magnesium ion / response to methylmercury / voltage-gated monoatomic cation channel activity / sleep / cellular response to dsRNA / dendritic spine organization / response to carbohydrate / regulation of monoatomic cation transmembrane transport / cellular response to lipid / locomotion / response to morphine / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / regulation of NMDA receptor activity / glutamate-gated calcium ion channel activity / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / calcium ion transmembrane import into cytosol / protein heterotetramerization / glutamate binding / neuromuscular process / cellular response to zinc ion / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / regulation of axonogenesis / male mating behavior / spinal cord development / dopamine metabolic process / suckling behavior / startle response / response to amine / monoatomic cation transmembrane transport / monoatomic cation transport / regulation of neuronal synaptic plasticity / modulation of excitatory postsynaptic potential / response to lithium ion / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / ligand-gated monoatomic ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / cellular response to manganese ion / calcium ion homeostasis / glutamate receptor binding / prepulse inhibition / multicellular organismal response to stress / monoatomic cation channel activity / long-term memory / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / sensory perception of pain / cell adhesion molecule binding / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / ionotropic glutamate receptor signaling pathway / excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.092 Å | |||||||||
Authors | Romero-Hernandez, A. / Tajima, N. / Chou, T. / 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6usu.cif.gz | 132.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6usu.ent.gz | 98.5 KB | Display | PDB format |
PDBx/mmJSON format | 6usu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6usu_validation.pdf.gz | 371.3 KB | Display | wwPDB validaton report |
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Full document | 6usu_full_validation.pdf.gz | 371.3 KB | Display | |
Data in XML | 6usu_validation.xml.gz | 1.8 KB | Display | |
Data in CIF | 6usu_validation.cif.gz | 8.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/us/6usu ftp://data.pdbj.org/pub/pdb/validation_reports/us/6usu | HTTPS FTP |
-Related structure data
Related structure data | 6usvC 6whrC 6whsC 6whtC 6whuC 6whvC 6whwC 6whxC 6whyC 6wi0C 6wi1C 4nf8S S: Starting model for refinement 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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Unit cell |
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-Components
#1: Protein | Mass: 33340.031 Da / Num. of mol.: 1 / Fragment: UNP residues 415-565, 684-821 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin1, Nmdar1 / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: P35439 |
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#2: Protein | Mass: 31785.299 Da / Num. of mol.: 1 / Fragment: UNP residues 402-539, 661-802 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin2a / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: Q00959 |
#3: Chemical | ChemComp-QGM / ( |
#4: Chemical | ChemComp-GLU / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.48 Å3/Da / Density % sol: 50.44 % |
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Crystal grow | Temperature: 291 K / Method: evaporation / pH: 7 Details: 0.2 M HEPES, pH 7.0, 60-90 mM sodium chloride, 15-20% PEG2000 MME |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 1.1 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Apr 6, 2013 |
Radiation | Monochromator: Double crystal cryo-cooled Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.1 Å / Relative weight: 1 |
Reflection | Resolution: 2.09→40 Å / Num. obs: 38873 / % possible obs: 99.9 % / Redundancy: 7.6 % / Biso Wilson estimate: 25.56 Å2 / Rmerge(I) obs: 0.117 / Net I/σ(I): 17.1 |
Reflection shell | Resolution: 2.09→2.18 Å / Redundancy: 6 % / Rmerge(I) obs: 0.62 / Num. unique obs: 3781 / CC1/2: 0.814 / % possible all: 99.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 4NF8 Resolution: 2.092→38.161 Å / SU ML: 0.23 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 21.77
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 77.3 Å2 / Biso mean: 27.2215 Å2 / Biso min: 12.93 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.092→38.161 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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