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Yorodumi- PDB-6mmw: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the '2-Knuck... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6mmw | |||||||||
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Title | Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the '2-Knuckle-Symmetric' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 | |||||||||
Components |
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Keywords | TRANSPORT PROTEIN / Ligand-gated Ion Channel / NMDA Receptor / ionotropic Glutamate Receptors / membrane protein | |||||||||
Function / homology | Function and homology information neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / response to environmental enrichment / 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 / regulation of cell communication / positive regulation of Schwann cell migration / response to environmental enrichment / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / serotonin metabolic process / conditioned place preference / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / response to other organism / positive regulation of inhibitory postsynaptic potential / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / cellular response to magnesium ion / response to methylmercury / voltage-gated monoatomic cation channel activity / sleep / cellular response to dsRNA / dendritic spine organization / response to carbohydrate / regulation of monoatomic cation transmembrane transport / cellular response to lipid / locomotion / response to morphine / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / regulation of NMDA receptor activity / glutamate-gated calcium ion channel activity / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / calcium ion transmembrane import into cytosol / protein heterotetramerization / glutamate binding / neuromuscular process / cellular response to zinc ion / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / regulation of axonogenesis / male mating behavior / spinal cord development / dopamine metabolic process / suckling behavior / startle response / response to amine / monoatomic cation transmembrane transport / monoatomic cation transport / regulation of neuronal synaptic plasticity / modulation of excitatory postsynaptic potential / response to lithium ion / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / ligand-gated monoatomic ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / cellular response to manganese ion / calcium ion homeostasis / glutamate receptor binding / prepulse inhibition / multicellular organismal response to stress / monoatomic cation channel activity / long-term memory / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / sensory perception of pain / cell adhesion molecule binding / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / ionotropic glutamate receptor signaling pathway / excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.2 Å | |||||||||
Authors | Jalali-Yazdi, F. / Chowdhury, S. / Yoshioka, C. / Gouaux, E. | |||||||||
Funding support | United States, 2items
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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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6mmw.cif.gz | 540.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6mmw.ent.gz | 450.7 KB | Display | PDB format |
PDBx/mmJSON format | 6mmw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6mmw_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6mmw_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 6mmw_validation.xml.gz | 90.3 KB | Display | |
Data in CIF | 6mmw_validation.cif.gz | 130.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mm/6mmw ftp://data.pdbj.org/pub/pdb/validation_reports/mm/6mmw | HTTPS FTP |
-Related structure data
Related structure data | 9164MC 9147C 9148C 9149C 9150C 9151C 9152C 9153C 9154C 9155C 9156C 9157C 9158C 9159C 9160C 9161C 9162C 9163C 9165C 6mm9C 6mmaC 6mmbC 6mmgC 6mmhC 6mmiC 6mmjC 6mmkC 6mmlC 6mmmC 6mmnC 6mmpC 6mmrC 6mmsC 6mmtC 6mmuC 6mmvC 6mmxC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-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 / Variant: 1a / Cell line (production host): TSA-201 / Organ (production host): Kidney / Production host: Homo sapiens (human) / References: UniProt: P35439 #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.) 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: Polysaccharide | Source method: isolated from a genetically manipulated source #4: Sugar | ChemComp-NAG / |
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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 |
-Sample preparation
Component | Name: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the '2-Knuckle-Symmetric' 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 | |||||||||||||||||||||||||
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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 |
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Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse | |||||||||||||||||||||||||
Specimen support | Details: unspecified | |||||||||||||||||||||||||
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 |
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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 / 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 | |||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 6.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 58461 / Algorithm: FOURIER SPACE / Symmetry type: POINT | |||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | |||||||||||||||||||||||||||||||||
Atomic model building |
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