[English] 日本語
Yorodumi- PDB-8e92: D-cycloserine and glutamate bound Human GluN1a-GluN2C NMDA recept... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8.0E+92 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | D-cycloserine and glutamate bound Human GluN1a-GluN2C NMDA receptor in intact conformation | |||||||||
Components |
| |||||||||
Keywords | TRANSPORT PROTEIN / Ligand-gated ion channel / ionotropic glutamate receptor / synaptic protein / voltage-gate ion channel | |||||||||
Function / homology | Function and homology information excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / glutamate-gated calcium ion channel activity / glutamate receptor signaling pathway / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors ...excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / glutamate-gated calcium ion channel activity / glutamate receptor signaling pathway / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / Neurexins and neuroligins / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / protein heterotetramerization / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / glycine binding / positive regulation of calcium ion transport into cytosol / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / positive regulation of excitatory postsynaptic potential / Long-term potentiation / monoatomic cation transport / ligand-gated monoatomic ion channel activity / neuromuscular process controlling balance / excitatory synapse / calcium ion homeostasis / synaptic cleft / EPHB-mediated forward signaling / excitatory postsynaptic potential / ionotropic glutamate receptor signaling pathway / regulation of membrane potential / Ras activation upon Ca2+ influx through NMDA receptor / positive regulation of synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / long-term synaptic potentiation / synaptic transmission, glutamatergic / postsynaptic density membrane / brain development / regulation of synaptic plasticity / visual learning / terminal bouton / negative regulation of protein catabolic process / response to wounding / synaptic vesicle / signaling receptor activity / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / calmodulin binding / neuron projection / dendrite / synapse / glutamatergic synapse / calcium ion binding / protein-containing complex binding / endoplasmic reticulum membrane / cell surface / positive regulation of transcription by RNA polymerase II / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.96 Å | |||||||||
Authors | Chou, T.-H. / Furukawa, H. | |||||||||
Funding support | United States, 2items
| |||||||||
Citation | Journal: Mol Cell / Year: 2022 Title: Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. Authors: Tsung-Han Chou / Hyunook Kang / Noriko Simorowski / Stephen F Traynelis / Hiro Furukawa / Abstract: Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. ...Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders. | |||||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8e92.cif.gz | 440.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8e92.ent.gz | 340.4 KB | Display | PDB format |
PDBx/mmJSON format | 8e92.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/e9/8e92 ftp://data.pdbj.org/pub/pdb/validation_reports/e9/8e92 | HTTPS FTP |
---|
-Related structure data
Related structure data | 27953MC 8e93C 8e94C 8e96C 8e97C 8e98C 8e99C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 95081.688 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRIN1, NMDAR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q05586 #2: Protein | Mass: 96958.406 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRIN2C, NMDAR2C / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q14957 #3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #4: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / Has ligand of interest | N | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Hetero-tetrameric GluN1a-GluN2C NMDA receptors / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
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 |
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 |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2800 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 57.6 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software | Name: cisTEM / Version: 1.0.2 / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.96 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 43478 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|