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- PDB-9bib: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, g... -
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Open data
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Basic information
Entry | Database: PDB / ID: 9bib | |||||||||
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Title | Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in open-channel conformation, C1 symmetry | |||||||||
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![]() | MEMBRANE PROTEIN / Ionotropic glutamate receptor / synaptic membrane protein | |||||||||
Function / homology | ![]() organelle / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange ...organelle / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / response to morphine / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / 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 / suckling behavior / startle response / response to amine / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / monoatomic cation transport / 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 / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / cellular response to manganese ion / glutamate receptor binding / long-term memory / positive regulation of synaptic transmission, glutamatergic / prepulse inhibition / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / response to fungicide / sensory perception of pain / 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 / adult locomotory behavior / regulation of membrane potential / excitatory postsynaptic potential / learning / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / response to calcium ion / visual learning / calcium channel activity / regulation of synaptic plasticity / terminal bouton / response to organic cyclic compound / memory / cerebral cortex development / synaptic vesicle membrane / intracellular calcium ion homeostasis / neuron cellular homeostasis / rhythmic process / calcium ion transport / synaptic vesicle / signaling receptor activity / presynaptic membrane / amyloid-beta binding / protein-containing complex assembly / chemical synaptic transmission / postsynaptic membrane / response to ethanol / negative regulation of neuron apoptotic process / transcription by RNA polymerase II / learning or memory / dendritic spine Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.81 Å | |||||||||
![]() | Chou, T.-H. / Furukawa, H. | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 493.7 KB | Display | ![]() |
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PDB format | ![]() | 365.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 44586MC ![]() 9areC ![]() 9arfC ![]() 9argC ![]() 9arhC ![]() 9ariC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() ![]() #2: Protein | Mass: 98888.945 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #3: Chemical | #4: Chemical | Has ligand of interest | Y | |
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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 |
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Sample preparation
Component | Name: Di-heterotetrameric GluN1-GluN2B NMDA receptors / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Value: 0.4 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
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 material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE / Humidity: 85 % / Chamber temperature: 285 K |
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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: ![]() |
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) |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1426240 | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 293641 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 9ARE Accession code: 9ARE / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||
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