[English] 日本語
Yorodumi
- EMDB-70920: Heteromeric GluA1/A2-CNIH1 in the activated state, composite map ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-70920
TitleHeteromeric GluA1/A2-CNIH1 in the activated state, composite map of LBD-TMD
Map dataGluA1A2-CNIH1 rr2b glu (composite map, LBD-TMD)
Sample
  • Complex: Heteromeric GluA1/A2-CNIH1 + rr2b + glu (LBD-TMD, composite map)
    • Protein or peptide: Isoform Flip of Glutamate receptor 1
    • Protein or peptide: Isoform Flip of Glutamate receptor 2
    • Protein or peptide: Protein cornichon homolog 1
  • Ligand: GLUTAMIC ACID
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
  • Ligand: N,N'-[biphenyl-4,4'-diyldi(2R)propane-2,1-diyl]dipropane-2-sulfonamide
  • Ligand: SODIUM ION
KeywordsGluA1A2-CNIH2 heterotetramer active iGluR / MEMBRANE PROTEIN
Function / homology
Function and homology information


Cargo concentration in the ER / axonal spine / positive regulation of locomotion involved in locomotory behavior / positive regulation of membrane potential / COPII-mediated vesicle transport / cellular response to ammonium ion / response to sucrose / myosin V binding / neuron spine / proximal dendrite ...Cargo concentration in the ER / axonal spine / positive regulation of locomotion involved in locomotory behavior / positive regulation of membrane potential / COPII-mediated vesicle transport / cellular response to ammonium ion / response to sucrose / myosin V binding / neuron spine / proximal dendrite / Cargo concentration in the ER / Trafficking of AMPA receptors / response to arsenic-containing substance / regulation of monoatomic ion transmembrane transport / cellular response to L-glutamate / cellular response to dsRNA / ligand-gated calcium channel activity / COPII-mediated vesicle transport / dendritic spine membrane / beta-2 adrenergic receptor binding / Synaptic adhesion-like molecules / long-term synaptic depression / cellular response to peptide hormone stimulus / spine synapse / dendritic spine neck / dendritic spine cytoplasm / cellular response to amine stimulus / dendritic spine head / response to psychosocial stress / peptide hormone receptor binding / response to morphine / Activation of AMPA receptors / spinal cord development / ligand-gated monoatomic cation channel activity / perisynaptic space / neuronal cell body membrane / protein kinase A binding / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / AMPA glutamate receptor activity / AMPA glutamate receptor clustering / behavioral response to pain / kainate selective glutamate receptor activity / immunoglobulin binding / adenylate cyclase binding / asymmetric synapse / AMPA glutamate receptor complex / response to electrical stimulus / regulation of receptor recycling / extracellularly glutamate-gated ion channel activity / cellular response to glycine / ionotropic glutamate receptor complex / Unblocking of NMDA receptors, glutamate binding and activation / G-protein alpha-subunit binding / glutamate receptor binding / conditioned place preference / positive regulation of synaptic transmission / long-term memory / postsynaptic density, intracellular component / response to fungicide / neuronal action potential / regulation of synaptic transmission, glutamatergic / extracellular ligand-gated monoatomic ion channel activity / vesicle-mediated transport / glutamate-gated receptor activity / cytoskeletal protein binding / cellular response to brain-derived neurotrophic factor stimulus / regulation of long-term synaptic depression / somatodendritic compartment / endoplasmic reticulum-Golgi intermediate compartment membrane / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / synapse assembly / excitatory synapse / ionotropic glutamate receptor signaling pathway / ionotropic glutamate receptor binding / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / dendrite cytoplasm / positive regulation of excitatory postsynaptic potential / dendritic shaft / SNARE binding / synaptic membrane / response to cocaine / PDZ domain binding / neuromuscular junction / cellular response to amino acid stimulus / establishment of protein localization / synaptic transmission, glutamatergic / protein tetramerization / ER to Golgi transport vesicle membrane / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / response to nutrient levels / cerebral cortex development / regulation of synaptic plasticity / receptor internalization / recycling endosome / postsynaptic density membrane / response to peptide hormone / cellular response to growth factor stimulus
Similarity search - Function
Cornichon / Cornichon, conserved site / Cornichon protein / Cornichon family signature. / Cornichon / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site ...Cornichon / Cornichon, conserved site / Cornichon protein / Cornichon family signature. / Cornichon / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I
Similarity search - Domain/homology
Protein cornichon homolog 1 / Glutamate receptor 1 / Glutamate receptor 2
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.76 Å
AuthorsYen LY / Newton TP / Gangwar SP / Sobolevsky AI
Funding support United States, 9 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)U24 GM129539 United States
Simons FoundationSF349247 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)U24 GM129541 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)F31NS132554 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS139087 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS083660 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS107253 United States
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)AR078814 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)CA206573 United States
CitationJournal: Nat Commun / Year: 2026
Title: Auxiliary subunits reshape structural asymmetry and functional plasticity in heterotetrameric GluA1/A2 AMPA receptor core.
Authors: Laura Y Yen / Thomas P Newton / Maria V Yelshanskaya / Muhammed Aktolun / Shanti Pal Gangwar / Rasmus P Clausen / Maria G Kurnikova / Alexander I Sobolevsky /
Abstract: AMPA-subtype ionotropic glutamate receptors (AMPARs) mediate the fast component of excitatory neurotransmission. They govern synaptic plasticity that underlies learning and memory, while their ...AMPA-subtype ionotropic glutamate receptors (AMPARs) mediate the fast component of excitatory neurotransmission. They govern synaptic plasticity that underlies learning and memory, while their dysregulation is implicated in numerous neurological disorders. The functional diversity of AMPARs arises from variations in their subunit composition and also their association with auxiliary subunits. While multiple structures of homomeric AMPARs have been reported, structural information for the heteromeric core - particularly in the absence of auxiliary subunits, which would serve as a functional and structural baseline - has been limited. Here, we report cryo-electron microscopy structures of GluA1/A2, the most abundant AMPAR di-heteromer in the brain, in the closed, open, and desensitized states. Using molecular dynamics (MD) simulations and cross-correlating structural and functional information, we find that auxiliary subunits increase the diameter of channel pore, which corresponds to larger conductance. Likewise, we find that recovery from desensitization slows with greater disruption of two-fold rotational symmetry of the ligand-binding domain dimer in the desensitized state. Both receptor activation and desensitization vary with the type and number of associated auxiliary proteins. These structures offer a foundation for uncovering how auxiliary subunits reshape structural asymmetry and functional plasticity in heterotetrameric AMPARs.
History
DepositionMay 31, 2025-
Header (metadata) releaseApr 8, 2026-
Map releaseApr 8, 2026-
UpdateApr 8, 2026-
Current statusApr 8, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_70920.png

Downloads & links

-
Map

FileDownload / File: emd_70920.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationGluA1A2-CNIH1 rr2b glu (composite map, LBD-TMD)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 416 pix.
= 345.28 Å		0.83 Å/pix.
x 416 pix.
= 345.28 Å		0.83 Å/pix.
x 416 pix.
= 345.28 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 4.7
Minimum - Maximum-30.522268 - 48.769165000000001
Average (Standard dev.)-0.0028124533 (±0.94661105)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions416416416
Spacing416416416
CellA=B=C: 345.28 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Sample components

-
Entire : Heteromeric GluA1/A2-CNIH1 + rr2b + glu (LBD-TMD, composite map)

EntireName: Heteromeric GluA1/A2-CNIH1 + rr2b + glu (LBD-TMD, composite map)
Components
  • Complex: Heteromeric GluA1/A2-CNIH1 + rr2b + glu (LBD-TMD, composite map)
    • Protein or peptide: Isoform Flip of Glutamate receptor 1
    • Protein or peptide: Isoform Flip of Glutamate receptor 2
    • Protein or peptide: Protein cornichon homolog 1
  • Ligand: GLUTAMIC ACID
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
  • Ligand: N,N'-[biphenyl-4,4'-diyldi(2R)propane-2,1-diyl]dipropane-2-sulfonamide
  • Ligand: SODIUM ION

-
Supramolecule #1: Heteromeric GluA1/A2-CNIH1 + rr2b + glu (LBD-TMD, composite map)

SupramoleculeName: Heteromeric GluA1/A2-CNIH1 + rr2b + glu (LBD-TMD, composite map)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 630 KDa

-
Macromolecule #1: Isoform Flip of Glutamate receptor 1

MacromoleculeName: Isoform Flip of Glutamate receptor 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 48.285328 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SVQNRTYIVT TILEDPYVML KKNANQFEGN DRYEGYCVEL AAEIAKHVGY SYRLEIVSDG KYGARDPDTK AWNGMVGELV YGRADVAVA PLTITLVREE VIDFSKPFMS LGISIMIKKP QKSKPGVFSF LDPLAYEIWM CIVFAYIGVS VVLFLVSRFS P YEWHSEEF ...String:
SVQNRTYIVT TILEDPYVML KKNANQFEGN DRYEGYCVEL AAEIAKHVGY SYRLEIVSDG KYGARDPDTK AWNGMVGELV YGRADVAVA PLTITLVREE VIDFSKPFMS LGISIMIKKP QKSKPGVFSF LDPLAYEIWM CIVFAYIGVS VVLFLVSRFS P YEWHSEEF EEGRDQTTSD QSNEFGIFNS LWFSLGAFMQ QGCDISPRSL SGRIVGGVWW FFTLIIISSY TANLAAFLTV ER MVSPIES AEDLAKQTEI AYGTLEAGST KEFFRRSKIA VFEKMWTYMK SAEPSVFVRT TEEGMIRVRK SKGKYAYLLE STM NEYIEQ RKPCDTMKVG GNLDSKGYGI ATPKGSALRG PVNLAVLKLS EQGVLDKLKS KWWYDKGECG SKDSGSKDKT SALS LSNVA GVFYILIGGL GLAMLVALIE FCYKSR

UniProtKB: Glutamate receptor 1

-
Macromolecule #2: Isoform Flip of Glutamate receptor 2

MacromoleculeName: Isoform Flip of Glutamate receptor 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 47.767008 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QKTVVVTTIL ESPYVMMKKN HEMLEGNERY EGYCVDLAAE IAKHCGFKYK LTIVGDGKYG ARDADTKIWN GMVGELVYGK ADIAIAPLT ITLVREEVID FSKPFMSLGI SIMIKKPQKS KPGVFSFLDP LAYEIWMCIV FAYIGVSVVL FLVSRFSPYE W HTEEFEDG ...String:
QKTVVVTTIL ESPYVMMKKN HEMLEGNERY EGYCVDLAAE IAKHCGFKYK LTIVGDGKYG ARDADTKIWN GMVGELVYGK ADIAIAPLT ITLVREEVID FSKPFMSLGI SIMIKKPQKS KPGVFSFLDP LAYEIWMCIV FAYIGVSVVL FLVSRFSPYE W HTEEFEDG RETQSSESTN EFGIFNSLWF SLGAFMRQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VS PIESAED LSKQTEIAYG TLDSGSTKEF FRRSKIAVFD KMWTYMRSAE PSVFVRTTAE GVARVRKSKG KYAYLLESTM NEY IEQRKP CDTMKVGGNL DSKGYGIATP KGSSLGTPVN LAVLKLSEQG VLDKLKNKWW YDKGECGAKD SGSKEKTSAL SLSN VAGVF YILVGGLGLA MLVALIEFCY KSR

UniProtKB: Glutamate receptor 2

-
Macromolecule #3: Protein cornichon homolog 1

MacromoleculeName: Protein cornichon homolog 1 / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 16.489604 KDa
SequenceString:
AFTFAAFCYM LALLLTAALI FFAIWHIIAF DELKTDYKNP IDQCNTLNPL VLPEYLIHAF FCVMFLCAAE WLTLGLNMPL LAYHIWRYM SRPVMSGPGL YDPTTIMNAD ILAYCQKEGW CKLAFYLLAF FYYLYGMIYV LVS

UniProtKB: Protein cornichon homolog 1

-
Macromolecule #4: GLUTAMIC ACID

MacromoleculeName: GLUTAMIC ACID / type: ligand / ID: 4 / Number of copies: 4 / Formula: GLU
Molecular weightTheoretical: 147.129 Da
Chemical component information

ChemComp-GLU:
GLUTAMIC ACID

-
Macromolecule #5: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...

MacromoleculeName: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
type: ligand / ID: 5 / Number of copies: 16 / Formula: POV
Molecular weightTheoretical: 760.076 Da
Chemical component information

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

-
Macromolecule #6: N,N'-[biphenyl-4,4'-diyldi(2R)propane-2,1-diyl]dipropane-2-sulfonamide

MacromoleculeName: N,N'-[biphenyl-4,4'-diyldi(2R)propane-2,1-diyl]dipropane-2-sulfonamide
type: ligand / ID: 6 / Number of copies: 2 / Formula: FWF
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 480.684 Da
Chemical component information

ChemComp-FWF:
N,N'-[biphenyl-4,4'-diyldi(2R)propane-2,1-diyl]dipropane-2-sulfonamide

-
Macromolecule #7: SODIUM ION

MacromoleculeName: SODIUM ION / type: ligand / ID: 7 / Number of copies: 1
Molecular weightTheoretical: 22.99 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration4.5 mg/mL
BufferpH: 8
Component:
ConcentrationFormulaName
150.0 mMNaClsodium chloride
20.0 mMC4H11NO3Tris-HCl
0.05 %C56H92O29digitonin
500.0 uMC14H14N2O2(R,R)-2b
1.0 mMC5H9NO4glutamate

Details: 150 mM NaCl, 20 mM Tris-HCl pH 8.0, and 0.05% digitonin, 500 uM (R,R)-2b, 1 mM glutamate
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Support film - Film thickness: 500 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 25 sec. / Pretreatment - Atmosphere: AIR / Details: 15 mA
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV
DetailsThe sample had compositional heterogeneity, with broken particles seen throughout. Otherwise, sample was monodisperse

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 47.03 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 5802290
CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER / Details: initial model from the experimental data
Final reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.76 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 76183
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more