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- EMDB-61623: Structure of native di-heteromeric GluN1-GluN2A NMDA receptor in ... -

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Basic information

Entry
Database: EMDB / ID: EMD-61623
TitleStructure of native di-heteromeric GluN1-GluN2A NMDA receptor in rat cortex and hippocampus
Map data
Sample
  • Complex: Native di-heterotetramer GluN1-GluN2A NMDA receptor in rat cortex and hippocampus
    • Complex: NMDA receptor
    • Complex: Fab
KeywordsMEMBRANE PROTEIN / native NMDA receptor / adult rat cartex and hippocampus / GluN2A / GluN2B
Biological speciesRattus norvegicus (Norway rat) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 9.8 Å
AuthorsZhang M / Feng J / Li Y / Zhu S
Funding support China, 1 items
OrganizationGrant numberCountry
Chinese Academy of Sciences China
CitationJournal: Cell / Year: 2025
Title: Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus.
Authors: Ming Zhang / Juan Feng / Chun Xie / Nan Song / Chaozhi Jin / Jian Wang / Qun Zhao / Lihua Zhang / Boshuang Wang / Yidi Sun / Fei Guo / Yang Li / Shujia Zhu /
Abstract: The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). ...The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus. Three major subtypes of GluN1-N2A-N2B, GluN1-N2B, and GluN1-N2A eNMDARs were resolved by cryoelectron microscopy (cryo-EM) at the resolution up to 4.2 Å. The particle ratio of these three subtypes was 9:7:4, indicating that about half of GluN2A and GluN2B subunits are incorporated into the tri-heterotetramers. Structural analysis revealed the asymmetric architecture of the GluN1-N2A-N2B receptor throughout the extracellular to the transmembrane layers. Moreover, the conformational variations between GluN1-N2B and GluN1-N2A-N2B receptors revealed the distinct biophysical properties across different eNMDAR subtypes. Our findings imply the structural and functional complexity of eNMDARs and shed light on structure-based therapeutic design targeting these eNMDARs in vivo.
History
DepositionSep 23, 2024-
Header (metadata) releaseFeb 5, 2025-
Map releaseFeb 5, 2025-
UpdateMar 19, 2025-
Current statusMar 19, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_61623.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

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AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 320 pix.
= 342.72 Å
1.07 Å/pix.
x 320 pix.
= 342.72 Å
1.07 Å/pix.
x 320 pix.
= 342.72 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.071 Å
Density
Contour LevelBy AUTHOR: 0.025
Minimum - Maximum-0.049772356 - 0.14178517
Average (Standard dev.)0.00083001045 (±0.01007527)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 342.72 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_61623_msk_1.map
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Half map: #1

Fileemd_61623_half_map_1.map
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Half map: #2

Fileemd_61623_half_map_2.map
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Sample components

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Entire : Native di-heterotetramer GluN1-GluN2A NMDA receptor in rat cortex...

EntireName: Native di-heterotetramer GluN1-GluN2A NMDA receptor in rat cortex and hippocampus
Components
  • Complex: Native di-heterotetramer GluN1-GluN2A NMDA receptor in rat cortex and hippocampus
    • Complex: NMDA receptor
    • Complex: Fab

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Supramolecule #1: Native di-heterotetramer GluN1-GluN2A NMDA receptor in rat cortex...

SupramoleculeName: Native di-heterotetramer GluN1-GluN2A NMDA receptor in rat cortex and hippocampus
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6

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Supramolecule #2: NMDA receptor

SupramoleculeName: NMDA receptor / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Rattus norvegicus (Norway rat)

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Supramolecule #3: Fab

SupramoleculeName: Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#6
Source (natural)Organism: Mus musculus (house mouse)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation statetissue

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: DIRECT ELECTRON DE-10 (5k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 9.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 21591
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

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