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Yorodumi- EMDB-3355: Activation of NMDA receptors and the mechanism of inhibition by i... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-3355 | |||||||||
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Title | Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Class X | |||||||||
Map data | Class X, unsharpened, unmasked map | |||||||||
Sample |
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Keywords | NMDA receptor / glutamate receptor / GluN1 / GluN2B / ion channel | |||||||||
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 | single particle reconstruction / cryo EM / Resolution: 6.25 Å | |||||||||
Authors | Tajima N / Karakas E / Grant T / Simorowski N / Diaz-Avalos R / Grigorieff N / Furukawa H | |||||||||
Citation | Journal: Nature / Year: 2016 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
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_3355.map.gz | 19.8 MB | EMDB map data format | |
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Header (meta data) | emd-3355-v30.xml emd-3355.xml | 11.8 KB 11.8 KB | Display Display | EMDB header |
Images | image_3355.png | 434.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-3355 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3355 | HTTPS FTP |
-Related structure data
Related structure data | 5fxjMC 3352C 3353C 3354C 3356C 5b3jC 5fxgC 5fxhC 5fxiC 5fxkC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_3355.map.gz / Format: CCP4 / Size: 62.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Class X, unsharpened, unmasked map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-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: Rattus norvegicus (Norway rat) / synonym: Rat / Location in cell: Plasma membane |
Molecular weight | Theoretical: 93 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) / Recombinant strain: Sf9 CRL-1711 / Recombinant cell: Sf9 / Recombinant plasmid: Modified pFL and pUCDM |
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: Rattus norvegicus (Norway rat) / synonym: Rat / Location in cell: Plasma membane |
Molecular weight | Theoretical: 92 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) / Recombinant strain: Sf9 CRL-1711 / Recombinant cell: Sf9 / Recombinant plasmid: Modified pFL and pUCDM |
Sequence | UniProtKB: Glutamate receptor ionotropic, NMDA 2B |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-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 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 38168 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / 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 |
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 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-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: 14000 |
-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: Coot |
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-5fxj: |