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- EMDB-3356: Activation of NMDA receptors and the mechanism of inhibition by i... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-3356 | |||||||||
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Title | Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Class Y | |||||||||
![]() | Class Y, unsharpened, unmasked map | |||||||||
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![]() | NMDA receptor / glutamate receptor / GluN1 / GluN2B / ion channel | |||||||||
Function / homology | ![]() cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / sensory organ development / pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / regulation of cAMP/PKA signal transduction / EPHB-mediated forward signaling / sensitization ...cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / sensory organ development / pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / regulation of cAMP/PKA signal transduction / EPHB-mediated forward signaling / sensitization / auditory behavior / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / response to other organism / protein localization to postsynaptic membrane / regulation of ARF protein signal transduction / fear response / transmitter-gated monoatomic ion channel activity / apical dendrite / response to carbohydrate / positive regulation of inhibitory postsynaptic potential / response to methylmercury / response to glycine / propylene metabolic process / response to manganese ion / interleukin-1 receptor binding / cellular response to dsRNA / cellular response to lipid / response to glycoside / positive regulation of glutamate secretion / negative regulation of dendritic spine maintenance / response to growth hormone / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / voltage-gated monoatomic cation channel activity / neurotransmitter receptor complex / NMDA selective glutamate receptor complex / heterocyclic compound binding / ligand-gated sodium channel activity / glutamate binding / response to morphine / regulation of axonogenesis / calcium ion transmembrane import into cytosol / neuromuscular process / regulation of dendrite morphogenesis / regulation of synapse assembly / protein heterotetramerization / male mating behavior / glycine binding / response to amine / receptor clustering / parallel fiber to Purkinje cell synapse / small molecule binding / suckling behavior / regulation of long-term synaptic depression / positive regulation of reactive oxygen species biosynthetic process / startle response / monoatomic cation transmembrane transport / social behavior / behavioral response to pain / positive regulation of calcium ion transport into cytosol / response to magnesium ion / associative learning / regulation of postsynaptic membrane potential / regulation of MAPK cascade / action potential / cellular response to glycine / extracellularly glutamate-gated ion channel activity / monoatomic cation transport / excitatory synapse / positive regulation of dendritic spine maintenance / positive regulation of excitatory postsynaptic potential / response to electrical stimulus / regulation of neuronal synaptic plasticity / monoatomic ion channel complex / cellular response to manganese ion / long-term memory / Unblocking of NMDA receptors, glutamate binding and activation / glutamate receptor binding / behavioral fear response / response to mechanical stimulus / detection of mechanical stimulus involved in sensory perception of pain / synaptic cleft / multicellular organismal response to stress / neuron development / prepulse inhibition / phosphatase binding / postsynaptic density, intracellular component / monoatomic cation channel activity / calcium ion homeostasis / response to fungicide / glutamate-gated receptor activity / D2 dopamine receptor binding / regulation of neuron apoptotic process Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.25 Å | |||||||||
![]() | Tajima N / Karakas E / Grant T / Simorowski N / Diaz-Avalos R / Grigorieff N / Furukawa H | |||||||||
![]() | ![]() Title: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. Authors: Nami Tajima / Erkan Karakas / Timothy Grant / Noriko Simorowski / Ruben Diaz-Avalos / Nikolaus Grigorieff / Hiro Furukawa / ![]() Abstract: The physiology of N-methyl-d-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed ...The physiology of N-methyl-d-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed mainly of GluN1 and GluN2 subunits. Activation of NMDA receptors requires binding of neurotransmitter agonists to a ligand-binding domain (LBD) and structural rearrangement of an amino-terminal domain (ATD). Recent crystal structures of GluN1-GluN2B NMDA receptors bound to agonists and an allosteric inhibitor, ifenprodil, represent the allosterically inhibited state. However, how the ATD and LBD move to activate the NMDA receptor ion channel remains unclear. Here we applied X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology to rat NMDA receptors to show that, in the absence of ifenprodil, the bi-lobed structure of GluN2 ATD adopts an open conformation accompanied by rearrangement of the GluN1-GluN2 ATD heterodimeric interface, altering subunit orientation in the ATD and LBD and forming an active receptor conformation that gates the ion channel. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 19.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.8 KB 11.8 KB | Display Display | ![]() |
Images | ![]() | 408.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 250.5 KB | Display | ![]() |
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Full document | ![]() | 249.6 KB | Display | |
Data in XML | ![]() | 6.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5fxkMC ![]() 3352C ![]() 3353C ![]() 3354C ![]() 3355C ![]() 5b3jC ![]() 5fxgC ![]() 5fxhC ![]() 5fxiC ![]() 5fxjC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Class Y, unsharpened, unmasked map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.31 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : NMDA Receptor
Entire | Name: NMDA Receptor |
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Components |
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-Supramolecule #1000: NMDA Receptor
Supramolecule | Name: NMDA Receptor / type: sample / ID: 1000 Details: The sample was purified in the presence of agonists Glycine and L-glutamate. Oligomeric state: One heterotetramer of 2 GluN1 and 2 GluN2B subunits Number unique components: 2 |
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Molecular weight | Theoretical: 370 KDa |
-Macromolecule #1: N-methyl-D-aspartate receptor GluN1
Macromolecule | Name: N-methyl-D-aspartate receptor GluN1 / type: protein_or_peptide / ID: 1 / Name.synonym: GluN1, NR1 / Number of copies: 2 / Oligomeric state: dimer / Recombinant expression: Yes |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 93 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: N-methyl-D-aspartate receptor GluN2B
Macromolecule | Name: N-methyl-D-aspartate receptor GluN2B / type: protein_or_peptide / ID: 2 / Name.synonym: GluN2B, NR2B / Number of copies: 2 / Oligomeric state: Dimer / Recombinant expression: Yes |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 92 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | UniProtKB: Glutamate receptor ionotropic, NMDA 2B |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 7 Details: 200 mM NaCl, 20 mM HEPES pH 7.0, 10 mM Glycine, 10 mM L-Glutamate, 0.002% MNG-3 |
Grid | Details: C-flat 1.2/1.3 Cu 400 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Instrument: FEI VITROBOT MARK II / Method: 3s Blot time |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Alignment procedure | Legacy - Electron beam tilt params: 0 |
Details | 21s exposure into 70 frames, with an exposure rate of ~8 electrons/pixel/s on the camera. |
Date | Aug 10, 2015 |
Image recording | Category: CCD / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Number real images: 1200 / Average electron dose: 100 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Calibrated magnification: 38168 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 22500 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
CTF correction | Details: Each Particle |
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Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Algorithm: OTHER / Resolution.type: BY AUTHOR / Resolution: 6.25 Å / Resolution method: OTHER / Software - Name: Unblur, CTFFIND4, FREALIGN Details: The highest resolution included in the refinement was 8A. Number images used: 15000 |
-Atomic model buiding 1
Initial model | PDB ID: Chain - #0 - Chain ID: A / Chain - #1 - Chain ID: B / Chain - #2 - Chain ID: C / Chain - #3 - Chain ID: D |
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Software | Name: ![]() |
Details | The individual domains were initially fitted using coot and real space refinement was performed using Phenix |
Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Target criteria: Real Space |
Output model | ![]() PDB-5fxk: |