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- PDB-8e96: Glycine and glutamate bound Human GluN1a-GluN2D NMDA receptor -

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Basic information

Entry
Database: PDB / ID: 8.0E+96
TitleGlycine and glutamate bound Human GluN1a-GluN2D NMDA receptor
Components
  • Glutamate receptor ionotropic, NMDA 1
  • Glutamate receptor ionotropic, NMDA 2D
KeywordsTRANSPORT PROTEIN / Ligand-gated ion channel / ionotropic glutamate receptor / synaptic protein / voltage-gate ion channel
Function / homology
Function and homology information


glycine-gated cation channel activity / regulation of sensory perception of pain / excitatory chemical synaptic transmission / Synaptic adhesion-like molecules / cellular response to L-glutamate / propylene metabolic process / response to glycine / Assembly and cell surface presentation of NMDA receptors / regulation of monoatomic cation transmembrane transport / Neurexins and neuroligins ...glycine-gated cation channel activity / regulation of sensory perception of pain / excitatory chemical synaptic transmission / Synaptic adhesion-like molecules / cellular response to L-glutamate / propylene metabolic process / response to glycine / Assembly and cell surface presentation of NMDA receptors / regulation of monoatomic cation transmembrane transport / Neurexins and neuroligins / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / voltage-gated monoatomic cation channel activity / glutamate binding / neurotransmitter receptor complex / ligand-gated sodium channel activity / calcium ion transmembrane import into cytosol / protein heterotetramerization / glycine binding / startle response / ligand-gated monoatomic ion channel activity / positive regulation of reactive oxygen species biosynthetic process / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / monoatomic cation transmembrane transport / positive regulation of calcium ion transport into cytosol / Long-term potentiation / regulation of neuronal synaptic plasticity / monoatomic cation transport / positive regulation of synaptic transmission, glutamatergic / synaptic cleft / calcium ion homeostasis / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / EPHB-mediated forward signaling / presynaptic active zone membrane / excitatory synapse / ionotropic glutamate receptor signaling pathway / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / Ras activation upon Ca2+ influx through NMDA receptor / synaptic membrane / positive regulation of excitatory postsynaptic potential / sodium ion transmembrane transport / hippocampal mossy fiber to CA3 synapse / adult locomotory behavior / excitatory postsynaptic potential / regulation of membrane potential / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / regulation of synaptic plasticity / brain development / visual learning / postsynaptic density membrane / calcium ion transmembrane transport / terminal bouton / synaptic vesicle / long-term synaptic potentiation / signaling receptor activity / amyloid-beta binding / RAF/MAP kinase cascade / dendritic spine / response to ethanol / chemical synaptic transmission / postsynaptic membrane / calmodulin binding / neuron projection / postsynaptic density / calcium ion binding / dendrite / synapse / endoplasmic reticulum membrane / protein-containing complex binding / glutamatergic synapse / cell surface / positive regulation of transcription by RNA polymerase II / plasma membrane / cytoplasm
Similarity search - Function
: / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. ...: / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Periplasmic binding protein-like II / Receptor, ligand binding region / Receptor family ligand binding region / D-Maltodextrin-Binding Protein; domain 2 / Periplasmic binding protein-like I / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
GLUTAMIC ACID / GLYCINE / Glutamate receptor ionotropic, NMDA 2D / Glutamate receptor ionotropic, NMDA 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.38 Å
AuthorsKang, H. / Furukawa, H.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS111745 United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)MH085926 United States
CitationJournal: Mol Cell / Year: 2022
Title: Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs.
Authors: Tsung-Han Chou / Hyunook Kang / Noriko Simorowski / Stephen F Traynelis / Hiro Furukawa /
Abstract: Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. ...Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders.
History
DepositionAug 26, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 7, 2022Provider: repository / Type: Initial release
Revision 1.1Dec 14, 2022Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first
Revision 1.2Nov 20, 2024Group: Data collection / Refinement description / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_3d_fitting_list / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id ..._em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type / _em_admin.last_update / _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Glutamate receptor ionotropic, NMDA 1
B: Glutamate receptor ionotropic, NMDA 2D
C: Glutamate receptor ionotropic, NMDA 1
D: Glutamate receptor ionotropic, NMDA 2D
hetero molecules


Theoretical massNumber of molelcules
Total (without water)381,44914
Polymers379,6774
Non-polymers1,77210
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Glutamate receptor ionotropic, NMDA 1 / GluN1 / Glutamate [NMDA] receptor subunit zeta-1 / N-methyl-D-aspartate receptor subunit NR1 / NMD-R1


Mass: 93078.250 Da / Num. of mol.: 2 / Mutation: C22S, R844N, R845G, K846A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRIN1, NMDAR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q05586
#2: Protein Glutamate receptor ionotropic, NMDA 2D / GluN2D / EB11 / Glutamate [NMDA] receptor subunit epsilon-4 / N-methyl D-aspartate receptor subtype ...GluN2D / EB11 / Glutamate [NMDA] receptor subunit epsilon-4 / N-methyl D-aspartate receptor subtype 2D / NMDAR2D / NR2D


Mass: 96760.492 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRIN2D, GluN2D, NMDAR2D / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O15399
#3: Chemical ChemComp-GLY / GLYCINE


Type: peptide linking / Mass: 75.067 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H5NO2 / Feature type: SUBJECT OF INVESTIGATION
#4: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#5: Chemical ChemComp-GLU / GLUTAMIC ACID


Type: L-peptide linking / Mass: 147.129 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C5H9NO4 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Hetero-tetrameric GluN1a-GluN2D NMDA receptors / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5
SpecimenConc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 85 % / Chamber temperature: 285 K

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 600 nm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 74.7 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

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Processing

SoftwareName: PHENIX / Version: 1.19.2_4158: / Classification: refinement
EM software
IDNameVersionCategory
4cryoSPARC3.3.2CTF correction
9cryoSPARC3.3.2initial Euler assignment
10cryoSPARC3.3.2final Euler assignment
12cryoSPARC3.3.23D reconstruction
13PHENIX1.19.2-4158model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 8012932
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.38 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 199693 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT
Atomic model building

3D fitting-ID: 1 / Source name: PDB / Type: experimental model

IDPDB-IDPdb chain-IDAccession codeInitial refinement model-ID
13OEL

3oel

A3OEL1
27SAA

7saa

7SAA2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00322384
ELECTRON MICROSCOPYf_angle_d0.52830368
ELECTRON MICROSCOPYf_dihedral_angle_d4.2383101
ELECTRON MICROSCOPYf_chiral_restr0.0443430
ELECTRON MICROSCOPYf_plane_restr0.0043918

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