[English] 日本語
Yorodumi- PDB-6whx: GluN1b-GluN2B NMDA receptor in complex with GluN2B antagonist SDZ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6whx | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | GluN1b-GluN2B NMDA receptor in complex with GluN2B antagonist SDZ 220-040, class 2 | |||||||||
Components |
| |||||||||
Keywords | MEMBRANE PROTEIN / NMDARs / Ligand-gated ion channels / METAL TRANSPORT / Ionotropic glutamate receptor / GluN2B antagonist | |||||||||
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 / apical dendrite / dendritic branch / regulation of respiratory gaseous exchange / positive regulation of inhibitory postsynaptic potential / response to other organism / protein localization to postsynaptic membrane / regulation of ARF protein signal transduction / response to methylmercury / fear response / propylene metabolic process / response to glycine / positive regulation of cysteine-type endopeptidase activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / interleukin-1 receptor binding / voltage-gated monoatomic cation channel activity / cellular response to lipid / regulation of monoatomic cation transmembrane transport / positive regulation of glutamate secretion / response to morphine / response to growth hormone / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / neuromuscular process / glutamate binding / protein heterotetramerization / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / regulation of axonogenesis / regulation of dendrite morphogenesis / positive regulation of calcium ion transport into cytosol / male mating behavior / glycine binding / heterocyclic compound binding / receptor clustering / suckling behavior / behavioral response to pain / startle response / response to amine / small molecule binding / action potential / : / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / associative learning / regulation of MAPK cascade / positive regulation of excitatory postsynaptic potential / social behavior / response to magnesium ion / cellular response to organic cyclic compound / ligand-gated monoatomic ion channel activity / extracellularly glutamate-gated ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / behavioral fear response / neuron development / postsynaptic density, intracellular component / cellular response to manganese ion / glutamate receptor binding / multicellular organismal response to stress / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / prepulse inhibition / D2 dopamine receptor binding / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / 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: 4.09 Å | |||||||||
Authors | Chou, T. / Tajima, N. / Furukawa, H. | |||||||||
Funding support | United States, 2items
| |||||||||
Citation | Journal: Cell / Year: 2020 Title: Structural Basis of Functional Transitions in Mammalian NMDA Receptors. Authors: Tsung-Han Chou / Nami Tajima / Annabel Romero-Hernandez / Hiro Furukawa / Abstract: Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of ...Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6whx.cif.gz | 524.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6whx.ent.gz | 405.9 KB | Display | PDB format |
PDBx/mmJSON format | 6whx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6whx_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6whx_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6whx_validation.xml.gz | 91 KB | Display | |
Data in CIF | 6whx_validation.cif.gz | 136.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wh/6whx ftp://data.pdbj.org/pub/pdb/validation_reports/wh/6whx | HTTPS FTP |
-Related structure data
Related structure data | 21679MC 6usuC 6usvC 6whrC 6whsC 6whtC 6whuC 6whvC 6whwC 6whyC 6wi0C 6wi1C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 108085.633 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P35439*PLUS #2: Protein | Mass: 98845.859 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q00960*PLUS #3: Sugar | #4: Chemical | Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: NMDA receptor GluN1b/2B functional ion channel complex Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | 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: 295 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 FIELD |
Image recording | Electron dose: 64.5 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software | Name: cisTEM / Version: 1.0.0 / Category: 3D reconstruction |
---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 4.09 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 109232 / Symmetry type: POINT |