[English] 日本語

- PDB-6mmx: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the 'Extende... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 6mmx | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the 'Extended' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 | |||||||||
![]() |
| |||||||||
![]() | TRANSPORT PROTEIN / Ligand-gated Ion Channel / NMDA Receptor / ionotropic Glutamate Receptors / membrane protein | |||||||||
Function / homology | ![]() neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / pons maturation / response to environmental enrichment / positive regulation of Schwann cell migration / regulation of cell communication / EPHB-mediated forward signaling ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / pons maturation / response to environmental enrichment / positive regulation of Schwann cell migration / regulation of cell communication / EPHB-mediated forward signaling / auditory behavior / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / serotonin metabolic process / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / response to other organism / protein localization to postsynaptic membrane / cellular response to magnesium ion / regulation of ARF protein signal transduction / transmitter-gated monoatomic ion channel activity / response to carbohydrate / positive regulation of inhibitory postsynaptic potential / sleep / response to methylmercury / locomotion / response to glycine / propylene metabolic process / dendritic spine organization / regulation of NMDA receptor activity / response to manganese ion / conditioned place preference / cellular response to dsRNA / cellular response to lipid / response to glycoside / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / voltage-gated monoatomic cation channel activity / neurotransmitter receptor complex / NMDA selective glutamate receptor complex / cellular response to zinc ion / ligand-gated sodium channel activity / glutamate binding / response to morphine / glutamate receptor signaling pathway / regulation of axonogenesis / calcium ion transmembrane import into cytosol / neuromuscular process / regulation of dendrite morphogenesis / regulation of synapse assembly / protein heterotetramerization / male mating behavior / glycine binding / spinal cord development / response to amine / parallel fiber to Purkinje cell synapse / suckling behavior / positive regulation of reactive oxygen species biosynthetic process / startle response / monoatomic cation transmembrane transport / dopamine metabolic process / social behavior / response to lithium ion / modulation of excitatory postsynaptic potential / positive regulation of calcium ion transport into cytosol / associative learning / regulation of postsynaptic membrane potential / action potential / response to light stimulus / cellular response to glycine / monoatomic cation transport / positive regulation of protein targeting to membrane / excitatory synapse / positive regulation of dendritic spine maintenance / positive regulation of excitatory postsynaptic potential / regulation of neuronal synaptic plasticity / monoatomic ion channel complex / cellular response to manganese ion / long-term memory / Unblocking of NMDA receptors, glutamate binding and activation / glutamate receptor binding / synaptic cleft / multicellular organismal response to stress / neuron development / prepulse inhibition / phosphatase binding / postsynaptic density, intracellular component / monoatomic cation channel activity / calcium ion homeostasis / response to fungicide / glutamate-gated receptor activity / regulation of neuron apoptotic process / cell adhesion molecule binding / presynaptic active zone membrane / glutamate-gated calcium ion channel activity / neurogenesis Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.99 Å | |||||||||
![]() | Jalali-Yazdi, F. / Chowdhury, S. / Yoshioka, C. / Gouaux, E. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 555.6 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 458.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.8 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.8 MB | Display | |
Data in XML | ![]() | 90.6 KB | Display | |
Data in CIF | ![]() | 132.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9165MC ![]() 9147C ![]() 9148C ![]() 9149C ![]() 9150C ![]() 9151C ![]() 9152C ![]() 9153C ![]() 9154C ![]() 9155C ![]() 9156C ![]() 9157C ![]() 9158C ![]() 9159C ![]() 9160C ![]() 9161C ![]() 9162C ![]() 9163C ![]() 9164C ![]() 6mm9C ![]() 6mmaC ![]() 6mmbC ![]() 6mmgC ![]() 6mmhC ![]() 6mmiC ![]() 6mmjC ![]() 6mmkC ![]() 6mmlC ![]() 6mmmC ![]() 6mmnC ![]() 6mmpC ![]() 6mmrC ![]() 6mmsC ![]() 6mmtC ![]() 6mmuC ![]() 6mmvC ![]() 6mmwC M: map data used to model this data C: citing same article ( |
---|---|
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.) ![]() ![]() ![]() #2: Protein | Mass: 93630.258 Da / Num. of mol.: 2 / Fragment: UNP residues 1-837 / Mutation: H128S, N687Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #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: Sugar | ChemComp-NAG / Has protein modification | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the 'Extended' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 Type: COMPLEX Details: Sample was heterologously expressed in TSA-201 cells, detergent solubilized, and affinity purified serially to obtain the triheteromeric receptor Entity ID: #1-#2 / Source: RECOMBINANT | |||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 0.5 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() | |||||||||||||||||||||||||
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: ![]() |
Electron lens | Mode: BRIGHT FIELD / 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: 1 / Num. of real images: 1891 |
-
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: 6.99 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 40881 / Algorithm: FOURIER SPACE / Symmetry type: POINT | |||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | |||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
|