+Open data
-Basic information
Entry | Database: PDB / ID: 9arg | |||||||||
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Title | Rat GluN1-GluN2B NMDA receptor channel in apo conformation | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Ligand-gated ion channel / ionotropic glutamate receptor / synaptic membrane protein | |||||||||
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 / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / 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 / apical dendrite / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / fear response / response to methylmercury / positive regulation of cysteine-type endopeptidase activity / voltage-gated monoatomic cation channel activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / NMDA glutamate receptor activity / response to morphine / positive regulation of glutamate secretion / response to growth hormone / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / 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 / heterocyclic compound binding / suckling behavior / receptor clustering / startle response / behavioral response to pain / response to amine / small molecule binding / regulation of neuronal synaptic plasticity / action potential / monoatomic cation transmembrane transport / monoatomic cation transport / associative learning / positive regulation of excitatory postsynaptic potential / regulation of MAPK cascade / response to magnesium ion / social behavior / ligand-gated monoatomic ion channel activity / cellular response to organic cyclic compound / excitatory synapse / extracellularly glutamate-gated ion channel activity / cellular response to glycine / positive regulation of dendritic spine maintenance / behavioral fear response / neuron development / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / postsynaptic density, intracellular component / cellular response to manganese ion / glutamate receptor binding / D2 dopamine receptor binding / multicellular organismal response to stress / long-term memory / positive regulation of synaptic transmission, glutamatergic / prepulse inhibition / monoatomic cation channel activity / detection of mechanical stimulus involved in sensory perception of pain / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / response to electrical stimulus / response to mechanical stimulus / glutamate-gated receptor activity Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.05 Å | |||||||||
Authors | Chou, T.-H. / Furukawa, H. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nature / Year: 2024 Title: Molecular mechanism of ligand gating and opening of NMDA receptor. Authors: Tsung-Han Chou / Max Epstein / Russell G Fritzemeier / Nicholas S Akins / Srinu Paladugu / Elijah Z Ullman / Dennis C Liotta / Stephen F Traynelis / Hiro Furukawa / Abstract: Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor ...Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor (NMDAR) is unique among all ligand-gated channels, requiring two ligands-glutamate and glycine-for activation. These receptors function as heterotetrameric ion channels, with the channel opening dependent on the simultaneous binding of glycine and glutamate to the extracellular ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, respectively. The exact molecular mechanism for channel gating by the two ligands has been unclear, particularly without structures representing the open channel and apo states. Here we show that the channel gate opening requires tension in the linker connecting the LBD and transmembrane domain (TMD) and rotation of the extracellular domain relative to the TMD. Using electron cryomicroscopy, we captured the structure of the GluN1-GluN2B (GluN1-2B) NMDAR in its open state bound to a positive allosteric modulator. This process rotates and bends the pore-forming helices in GluN1 and GluN2B, altering the symmetry of the TMD channel from pseudofourfold to twofold. Structures of GluN1-2B NMDAR in apo and single-liganded states showed that binding of either glycine or glutamate alone leads to distinct GluN1-2B dimer arrangements but insufficient tension in the LBD-TMD linker for channel opening. This mechanistic framework identifies a key determinant for channel gating and a potential pharmacological strategy for modulating NMDAR activity. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9arg.cif.gz | 514.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb9arg.ent.gz | 393 KB | Display | PDB format |
PDBx/mmJSON format | 9arg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ar/9arg ftp://data.pdbj.org/pub/pdb/validation_reports/ar/9arg | HTTPS FTP |
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-Related structure data
Related structure data | 43781MC 9areC 9arfC 9arhC 9ariC 9bibC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 95225.883 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin1, Nmdar1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P35439 #2: Protein | Mass: 98888.945 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin2b / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q00960 |
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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: Di-heterotetrameric GluN1-GluN2B NMDA receptors / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.400 MDa / Experimental value: NO |
Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 85 % / Chamber temperature: 285 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 FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 66.3 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: NONE | |||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.05 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 60195 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||
Atomic model building | Protocol: BACKBONE TRACE | |||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7SAA Accession code: 7SAA / Source name: PDB / Type: experimental model | |||||||||||||||||||||||||||||||||
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