[English] 日本語
Yorodumi
- PDB-9ovv: Heteromeric GluA1/A2-CNIH1 in the activated state, composite map ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9ovv
TitleHeteromeric GluA1/A2-CNIH1 in the activated state, composite map of LBD-TMD
Components
  • (Isoform Flip of Glutamate receptor ...) x 2
  • Protein cornichon homolog 1
KeywordsMEMBRANE PROTEIN / GluA1A2-CNIH2 heterotetramer active iGluR
Function / homology
Function and homology information


Cargo concentration in the ER / cellular response to ammonium ion / axonal spine / positive regulation of locomotion involved in locomotory behavior / COPII-mediated vesicle transport / positive regulation of membrane potential / response to sucrose / regulation of monoatomic ion transmembrane transport / myosin V binding / neuron spine ...Cargo concentration in the ER / cellular response to ammonium ion / axonal spine / positive regulation of locomotion involved in locomotory behavior / COPII-mediated vesicle transport / positive regulation of membrane potential / response to sucrose / regulation of monoatomic ion transmembrane transport / myosin V binding / neuron spine / Trafficking of AMPA receptors / proximal dendrite / Cargo concentration in the ER / response to arsenic-containing substance / cellular response to L-glutamate / cellular response to dsRNA / long-term synaptic depression / ligand-gated calcium channel activity / COPII-mediated vesicle transport / dendritic spine membrane / beta-2 adrenergic receptor binding / Synaptic adhesion-like molecules / cellular response to peptide hormone stimulus / spine synapse / dendritic spine neck / dendritic spine cytoplasm / dendritic spine head / cellular response to amine stimulus / response to morphine / peptide hormone receptor binding / response to psychosocial stress / Activation of AMPA receptors / ligand-gated monoatomic cation channel activity / perisynaptic space / spinal cord development / neuronal cell body membrane / Trafficking of GluR2-containing AMPA receptors / protein kinase A binding / response to lithium ion / AMPA glutamate receptor activity / AMPA glutamate receptor clustering / regulation of receptor recycling / kainate selective glutamate receptor activity / behavioral response to pain / immunoglobulin binding / adenylate cyclase binding / AMPA glutamate receptor complex / extracellularly glutamate-gated ion channel activity / cellular response to glycine / response to electrical stimulus / ionotropic glutamate receptor complex / asymmetric synapse / Unblocking of NMDA receptors, glutamate binding and activation / G-protein alpha-subunit binding / glutamate receptor binding / positive regulation of synaptic transmission / conditioned place preference / long-term memory / postsynaptic density, intracellular component / regulation of synaptic transmission, glutamatergic / response to fungicide / neuronal action potential / cytoskeletal protein binding / extracellular ligand-gated monoatomic ion channel activity / vesicle-mediated transport / glutamate-gated receptor activity / cellular response to brain-derived neurotrophic factor stimulus / regulation of long-term synaptic depression / endoplasmic reticulum-Golgi intermediate compartment membrane / somatodendritic compartment / glutamate-gated calcium ion channel activity / synapse assembly / presynaptic active zone membrane / ionotropic glutamate receptor signaling pathway / ionotropic glutamate receptor binding / dendrite cytoplasm / excitatory synapse / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of excitatory postsynaptic potential / cellular response to amino acid stimulus / dendritic shaft / SNARE binding / synaptic membrane / response to cocaine / PDZ domain binding / neuromuscular junction / protein tetramerization / establishment of protein localization / ER to Golgi transport vesicle membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / receptor internalization / cerebral cortex development / regulation of synaptic plasticity / response to nutrient levels / cellular response to growth factor stimulus / recycling endosome / postsynaptic density membrane / modulation of chemical synaptic transmission
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
Chem-FWF / GLUTAMIC ACID / Chem-POV / Protein cornichon homolog 1 / Glutamate receptor 1 / Glutamate receptor 2
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.76 Å
AuthorsYen, L.Y. / Newton, T.P. / Gangwar, S.P. / Sobolevsky, A.I.
Funding support United States, 9items
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, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 8, 2026Provider: repository / Type: Initial release
Revision 1.0Apr 8, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Apr 8, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Apr 8, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1May 20, 2026Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.journal_volume / _citation_author.identifier_ORCID / _em_admin.last_update
Revision 1.1May 20, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin / Data content type: EM metadata / EM metadata / EM metadata
Item: _citation.journal_volume / _citation_author.identifier_ORCID / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform Flip of Glutamate receptor 1
B: Isoform Flip of Glutamate receptor 2
C: Isoform Flip of Glutamate receptor 1
D: Isoform Flip of Glutamate receptor 2
E: Protein cornichon homolog 1
F: Protein cornichon homolog 1
G: Protein cornichon homolog 1
H: Protein cornichon homolog 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)271,79731
Polymers258,0638
Non-polymers13,73423
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

-
Isoform Flip of Glutamate receptor ... , 2 types, 4 molecules ACBD

#1: Protein Isoform Flip of Glutamate receptor 1 / GluR-1 / AMPA-selective glutamate receptor 1 / GluR-A / GluR-K1 / Glutamate receptor ionotropic / AMPA 1


Mass: 48285.328 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gria1, GluA1, Glur1 / Plasmid: pEG BacMam / Cell (production host): epithelial / Cell line (production host): HEK 293S GntI- / Organ (production host): kidney / Production host: Homo sapiens (human) / Tissue (production host): kidney / References: UniProt: P19490
#2: Protein Isoform Flip of Glutamate receptor 2 / GluR-2 / AMPA-selective glutamate receptor 2 / GluR-B / GluR-K2 / Glutamate receptor ionotropic / AMPA 2


Mass: 47767.008 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gria2, GluA2, Glur2 / Plasmid: pEG BacMam / Cell (production host): epithelial / Cell line (production host): HEK 293S GntI- / Organ (production host): kidney / Production host: Homo sapiens (human) / Tissue (production host): kidney / References: UniProt: P19491

-
Protein , 1 types, 4 molecules EFGH

#3: Protein
Protein cornichon homolog 1 / CNIH-1 / Cornichon family AMPA receptor auxiliary protein 1 / Protein cornichon homolog / T-cell ...CNIH-1 / Cornichon family AMPA receptor auxiliary protein 1 / Protein cornichon homolog / T-cell growth-associated molecule 77 / TGAM77


Mass: 16489.604 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O95406

-
Non-polymers , 4 types, 23 molecules

#4: Chemical
ChemComp-GLU / GLUTAMIC ACID


Type: L-peptide linking / Mass: 147.129 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C5H9NO4 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical
ChemComp-POV / (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / POPC


Mass: 760.076 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: C42H82NO8P / Comment: phospholipid*YM
#6: Chemical ChemComp-FWF / N,N'-[biphenyl-4,4'-diyldi(2R)propane-2,1-diyl]dipropane-2-sulfonamide / GluR-1 / AMPA-selective glutamate receptor 1 / GluR-A / GluR-K1 / Glutamate receptor ionotropic / AMPA 1


Mass: 480.684 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C24H36N2O4S2 / Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gria1, GluA1, Glur1 / Plasmid: pEG BacMam / Cell (production host): epithelial / Cell line (production host): HEK 293S GntI- / Organ (production host): kidney / Production host: Homo sapiens (human) / Tissue (production host): kidney / Feature type: SUBJECT OF INVESTIGATION
#7: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Heteromeric GluA1/A2-CNIH1 + rr2b + glu (LBD-TMD, composite map)
Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Molecular weightValue: 0.63 MDa / Experimental value: NO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Source (recombinant)Organism: Homo sapiens (human) / Strain: HEK 293S GntI- / Plasmid: pEG BacMam
Buffer solutionpH: 8
Details: 150 mM NaCl, 20 mM Tris-HCl pH 8.0, and 0.05% digitonin, 500 uM (R,R)-2b, 1 mM glutamate
Buffer component
IDConc.NameFormulaBuffer-ID
1150 mMsodium chlorideNaCl1
220 mMTris-HClC4H11NO31
30.05 %digitoninC56H92O291
4500 uM(R,R)-2bC14H14N2O21
51 mMglutamateC5H9NO41
SpecimenConc.: 4.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: The sample had compositional heterogeneity, with broken particles seen throughout. Otherwise, sample was monodisperse
Specimen supportDetails: 15 mA / Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm
Image recordingElectron dose: 47.03 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2PHENIX1.11.1_2575model refinement
5cryoSPARCCTF correction
10cryoSPARCinitial Euler assignment
11cryoSPARCfinal Euler assignment
12cryoSPARCclassification
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 5802290
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 3.76 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 76183 / Symmetry type: POINT
RefinementStereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00536198
ELECTRON MICROSCOPYf_angle_d0.77364868
ELECTRON MICROSCOPYf_dihedral_angle_d9.814848
ELECTRON MICROSCOPYf_chiral_restr0.0452690
ELECTRON MICROSCOPYf_plane_restr0.0055220

+
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