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- PDB-6mmb: Diheteromeric NMDA receptor GluN1/GluN2A in the 'Super-Splayed' c... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6mmb | |||||||||
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Title | Diheteromeric NMDA receptor GluN1/GluN2A in the 'Super-Splayed' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 6.1 | |||||||||
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![]() | 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 / response to environmental enrichment / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / serotonin metabolic process / conditioned place preference / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / response to other organism / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / positive regulation of inhibitory postsynaptic potential / propylene metabolic process / response to glycine / cellular response to magnesium ion / regulation of ARF protein signal transduction / sleep / response to methylmercury / voltage-gated monoatomic cation channel activity / dendritic spine organization / cellular response to dsRNA / response to carbohydrate / regulation of monoatomic cation transmembrane transport / cellular response to lipid / response to morphine / NMDA glutamate receptor activity / locomotion / regulation of NMDA receptor activity / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / calcium ion transmembrane import into cytosol / cellular response to zinc ion / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / dopamine metabolic process / spinal cord development / suckling behavior / action potential / startle response / response to amine / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / modulation of excitatory postsynaptic potential / monoatomic cation transport / response to lithium ion / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / ligand-gated monoatomic ion channel activity / excitatory synapse / cellular response to glycine / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / neuron development / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / postsynaptic density, intracellular component / phosphatase binding / cellular response to manganese ion / glutamate receptor binding / multicellular organismal response to stress / long-term memory / prepulse inhibition / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated calcium ion channel activity / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / cell adhesion molecule binding / sensory perception of pain / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / neurogenesis Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 12.7 Å | |||||||||
![]() | Jalali-Yazdi, F. / Chowdhury, S. / Yoshioka, C. / Gouaux, E. | |||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 524.6 KB | Display | ![]() |
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PDB format | ![]() | 420.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9149MC ![]() 9147C ![]() 9148C ![]() 9150C ![]() 9151C ![]() 9152C ![]() 9153C ![]() 9154C ![]() 9155C ![]() 9156C ![]() 9157C ![]() 9158C ![]() 9159C ![]() 9160C ![]() 9161C ![]() 9162C ![]() 9163C ![]() 9164C ![]() 9165C ![]() 6mm9C ![]() 6mmaC ![]() 6mmgC ![]() 6mmhC ![]() 6mmiC ![]() 6mmjC ![]() 6mmkC ![]() 6mmlC ![]() 6mmmC ![]() 6mmnC ![]() 6mmpC ![]() 6mmrC ![]() 6mmsC ![]() 6mmtC ![]() 6mmuC ![]() 6mmvC ![]() 6mmwC ![]() 6mmxC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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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.) ![]() ![]() ![]() #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.) ![]() ![]() ![]() #3: 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 |
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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 micromolar zinc chloride, and at pH 6.1 Type: COMPLEX Details: Sample was heterologously expressed in TSA-201 cells, detergent solubilized, and affinity purified Entity ID: #1-#2 / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Value: 0.5 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 6.1 | |||||||||||||||||||||||||
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 | 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. |
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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: ![]() |
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: 2163 |
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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: 12.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 10238 / Algorithm: FOURIER SPACE / Symmetry type: POINT | |||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | |||||||||||||||||||||||||||||||||
Atomic model building |
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