[English] 日本語
Yorodumi- PDB-6mmj: Diheteromeric NMDA receptor GluN1/GluN2A in the 'Super-Splayed' c... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6mmj | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Diheteromeric NMDA receptor GluN1/GluN2A in the 'Super-Splayed' conformation, in complex with glycine and glutamate, in the presence of 1 millimolar zinc chloride, and at pH 7.4 | |||||||||
Components |
| |||||||||
Keywords | TRANSPORT PROTEIN / Ligand-gated Ion Channel / NMDA Receptor / ionotropic Glutamate Receptors / membrane protein | |||||||||
Function / homology | Function and homology information response to ammonium ion / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / serotonin metabolic process / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion ...response to ammonium ion / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / serotonin metabolic process / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / protein localization to postsynaptic membrane / dendritic branch / regulation of respiratory gaseous exchange / propylene metabolic process / response to glycine / response to other organism / sleep / cellular response to magnesium ion / response to methylmercury / voltage-gated monoatomic cation channel activity / locomotion / response to morphine / glutamate-gated calcium ion channel activity / cellular response to dsRNA / regulation of monoatomic cation transmembrane transport / response to carbohydrate / dendritic spine organization / cellular response to lipid / NMDA glutamate receptor activity / 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 / protein heterotetramerization / response to manganese ion / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / neuromuscular process / cellular response to zinc ion / startle response / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of neuronal synaptic plasticity / dopamine metabolic process / male mating behavior / regulation of dendrite morphogenesis / regulation of axonogenesis / spinal cord development / suckling behavior / monoatomic cation transmembrane transport / response to amine / regulation of NMDA receptor activity / social behavior / ligand-gated monoatomic ion channel activity / monoatomic cation transport / positive regulation of excitatory postsynaptic potential / associative learning / excitatory synapse / positive regulation of dendritic spine maintenance / response to light stimulus / Unblocking of NMDA receptors, glutamate binding and activation / long-term memory / regulation of postsynaptic membrane potential / glutamate receptor binding / phosphatase binding / calcium ion homeostasis / synaptic cleft / cellular response to manganese ion / prepulse inhibition / regulation of neuron apoptotic process / presynaptic active zone membrane / response to amphetamine / response to fungicide / monoatomic cation channel activity / glutamate-gated receptor activity / sensory perception of pain / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / hippocampal mossy fiber to CA3 synapse / excitatory postsynaptic potential / regulation of membrane potential / ionotropic glutamate receptor signaling pathway / cell adhesion molecule binding / neurogenesis / adult locomotory behavior / positive regulation of synaptic transmission, glutamatergic / response to cocaine / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / learning / synaptic transmission, glutamatergic / long-term synaptic potentiation / hippocampus development / cellular response to amino acid stimulus / postsynaptic density membrane / visual learning / regulation of long-term neuronal synaptic plasticity Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 16.5 Å | |||||||||
Authors | Jalali-Yazdi, F. / Chowdhury, S. / Yoshioka, C. / Gouaux, E. | |||||||||
Funding support | United States, 2items
| |||||||||
Citation | Journal: Cell / Year: 2018 Title: Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. Authors: Farzad Jalali-Yazdi / Sandipan Chowdhury / Craig Yoshioka / Eric Gouaux / Abstract: N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to ...N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to schizophrenia. Zinc and pH are physiological allosteric modulators of NMDARs, with GluN2A-containing receptors inhibited by nanomolar concentrations of divalent zinc and by excursions to low pH. Despite the widespread importance of zinc and proton modulation of NMDARs, the molecular mechanism by which these ions modulate receptor activity has proven elusive. Here, we use cryoelectron microscopy to elucidate the structure of the GluN1/GluN2A NMDAR in a large ensemble of conformations under a range of physiologically relevant zinc and proton concentrations. We show how zinc binding to the amino terminal domain elicits structural changes that are transduced though the ligand-binding domain and result in constriction of the ion channel gate. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6mmj.cif.gz | 531.5 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6mmj.ent.gz | 430.2 KB | Display | PDB format |
PDBx/mmJSON format | 6mmj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mm/6mmj ftp://data.pdbj.org/pub/pdb/validation_reports/mm/6mmj | HTTPS FTP |
---|
-Related structure data
Related structure data | 9153MC 9147C 9148C 9149C 9150C 9151C 9152C 9154C 9155C 9156C 9157C 9158C 9159C 9160C 9161C 9162C 9163C 9164C 9165C 6mm9C 6mmaC 6mmbC 6mmgC 6mmhC 6mmiC 6mmkC 6mmlC 6mmmC 6mmnC 6mmpC 6mmrC 6mmsC 6mmtC 6mmuC 6mmvC 6mmwC 6mmxC 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: 94189.781 Da / Num. of mol.: 2 / Fragment: UNP residues 1-838 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin1, Nmdar1 / Cell line (production host): TSA-201 / Organ (production host): Kidney / Production host: Homo sapiens (human) / References: UniProt: P35439 #2: Protein | Mass: 93740.352 Da / Num. of mol.: 2 / Fragment: UNP residues 1-837 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin2a / Cell line (production host): TSA-201 / Organ (production host): Kidney / Production host: Homo sapiens (human) / References: UniProt: Q00959 #3: Sugar | ChemComp-NAG / |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Diheteromeric NMDA receptor GluN1/GluN2A in the 'Super-Splayed' conformation, in complex with glycine and glutamate, in the presence of 1 milliomolar zinc chloride, and at pH 7.4 Type: COMPLEX Details: Sample was heterologously expressed in TSA-201 cells, detergent solubilized, and affinity purified Entity ID: #1-#2 / Source: RECOMBINANT | |||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 0.5 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: Rattus norvegicus (Norway rat) | |||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Cell: TSA-201 | |||||||||||||||||||||||||
Buffer solution | pH: 7.4 | |||||||||||||||||||||||||
Buffer component |
| |||||||||||||||||||||||||
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse | |||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 291 K / Details: sample was blotted for 3 seconds at blot force 1. |
-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 / Cs: 2.7 mm |
Image recording | Average exposure time: 22 sec. / Electron dose: 52 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 1068 |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | |||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| |||||||||||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 16.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 6081 / Algorithm: FOURIER SPACE / Symmetry type: POINT | |||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | |||||||||||||||||||||||||||||||||
Atomic model building |
|