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- PDB-6usu: Crystal structure of GluN1/GluN2A ligand-binding domain in comple... -
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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 | |||||||||
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![]() | METAL TRANSPORT / NMDARs / LBD / Ion channels | |||||||||
Function / homology | ![]() neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / serotonin metabolic process / conditioned place preference / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / 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 / propylene metabolic process / response to glycine / cellular response to magnesium ion / regulation of ARF protein signal transduction / sleep / response to methylmercury / voltage-gated monoatomic cation channel activity / cellular response to dsRNA / dendritic spine organization / response to carbohydrate / regulation of monoatomic cation transmembrane transport / locomotion / cellular response to lipid / response to morphine / NMDA glutamate receptor activity / regulation of NMDA receptor activity / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / calcium ion transmembrane import into cytosol / cellular response to zinc ion / 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 / dopamine metabolic process / spinal cord development / action potential / suckling behavior / startle response / response to amine / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / 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 / excitatory synapse / cellular response to glycine / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / neuron development / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / postsynaptic density, intracellular component / phosphatase binding / cellular response to manganese ion / glutamate-gated calcium ion channel activity / glutamate receptor binding / multicellular organismal response to stress / prepulse inhibition / monoatomic cation channel activity / long-term memory / calcium ion homeostasis / 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 / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Romero-Hernandez, A. / Tajima, N. / Chou, T. / Furukawa, H. | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 132.3 KB | Display | ![]() |
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PDB format | ![]() | 98.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 371.3 KB | Display | ![]() |
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Full document | ![]() | 371.3 KB | Display | |
Data in XML | ![]() | 1.8 KB | Display | |
Data in CIF | ![]() | 8.9 KB | Display | |
Arichive directory | ![]() ![]() | 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 ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() ![]() |
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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.) ![]() ![]() ![]() ![]() |
#3: Chemical | ChemComp-QGM / ( |
#4: Chemical | ChemComp-GLU / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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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: ![]() ![]() ![]() |
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 |
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Processing
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Refinement | Method to determine structure: ![]() 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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