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- EMDB-74381: The LBD-TMD structure of native mouse AMPAR with 3 TARPs 1 CNIH -

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Basic information

Entry
Database: EMDB / ID: EMD-74381
TitleThe LBD-TMD structure of native mouse AMPAR with 3 TARPs 1 CNIH
Map data
Sample
  • Complex: native mouse AMPAR
    • Protein or peptide: Glutamate receptor 1
    • Protein or peptide: Glutamate receptor 2
    • Protein or peptide: Protein cornichon homolog 2
    • Protein or peptide: Voltage-dependent calcium channel gamma-2 subunit
    • Protein or peptide: Voltage-dependent calcium channel gamma-8 subunit
  • Ligand: PALMITIC ACID
  • Ligand: (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
KeywordsiGluR / AMPA receptors / SIGNALING PROTEIN
Function / homology
Function and homology information


negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Activation of AMPA receptors / Cargo concentration in the ER / COPII-mediated vesicle transport / Presynaptic depolarization and calcium channel opening / Synaptic adhesion-like molecules / LGI-ADAM interactions ...negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Activation of AMPA receptors / Cargo concentration in the ER / COPII-mediated vesicle transport / Presynaptic depolarization and calcium channel opening / Synaptic adhesion-like molecules / LGI-ADAM interactions / Unblocking of NMDA receptors, glutamate binding and activation / Trafficking of GluR2-containing AMPA receptors / axonal spine / positive regulation of locomotion involved in locomotory behavior / Trafficking of AMPA receptors / localization within membrane / positive regulation of membrane potential / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / cellular response to ammonium ion / response to sucrose / L-type voltage-gated calcium channel complex / myosin V binding / cerebellar mossy fiber / neuron spine / postsynaptic neurotransmitter receptor diffusion trapping / proximal dendrite / regulation of AMPA receptor activity / protein phosphatase 2B binding / response to arsenic-containing substance / regulation of monoatomic ion transmembrane transport / channel regulator activity / cellular response to L-glutamate / ligand-gated calcium channel activity / cellular response to dsRNA / membrane hyperpolarization / nervous system process / dendritic spine membrane / beta-2 adrenergic receptor binding / long-term synaptic depression / protein targeting to membrane / cellular response to peptide hormone stimulus / voltage-gated calcium channel complex / cellular response to amine stimulus / peptide hormone receptor binding / response to psychosocial stress / neurotransmitter receptor localization to postsynaptic specialization membrane / response to morphine / perisynaptic space / spinal cord development / neuronal cell body membrane / neuromuscular junction development / protein kinase A binding / response to lithium ion / AMPA glutamate receptor activity / transmission of nerve impulse / immunoglobulin binding / adenylate cyclase binding / behavioral response to pain / AMPA glutamate receptor complex / regulation of receptor recycling / response to electrical stimulus / ionotropic glutamate receptor complex / asymmetric synapse / G-protein alpha-subunit binding / glutamate receptor binding / membrane depolarization / conditioned place preference / positive regulation of synaptic transmission / regulation of postsynaptic membrane neurotransmitter receptor levels / long-term memory / voltage-gated calcium channel activity / postsynaptic density, intracellular component / response to fungicide / neuronal action potential / vesicle-mediated transport / glutamate-gated receptor activity / cellular response to brain-derived neurotrophic factor stimulus / positive regulation of synaptic transmission, glutamatergic / somatodendritic compartment / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / synapse assembly / excitatory synapse / ionotropic glutamate receptor binding / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse / dendritic shaft / synaptic membrane / PDZ domain binding / calcium channel regulator activity / response to cocaine / neuromuscular junction / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic transmission, glutamatergic / regulation of membrane potential / response to nutrient levels / cerebral cortex development
Similarity search - Function
Cornichon / Cornichon, conserved site / Cornichon protein / Cornichon family signature. / Cornichon / Voltage-dependent calcium channel, gamma-8 subunit / Voltage-dependent calcium channel, gamma-2 subunit / : / PMP-22/EMP/MP20/Claudin family / Voltage-dependent calcium channel, gamma subunit ...Cornichon / Cornichon, conserved site / Cornichon protein / Cornichon family signature. / Cornichon / Voltage-dependent calcium channel, gamma-8 subunit / Voltage-dependent calcium channel, gamma-2 subunit / : / PMP-22/EMP/MP20/Claudin family / Voltage-dependent calcium channel, gamma subunit / PMP-22/EMP/MP20/Claudin superfamily / 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
Glutamate receptor / Protein cornichon homolog 2 / Voltage-dependent calcium channel gamma-2 subunit / Glutamate receptor 1 / Voltage-dependent calcium channel gamma-8 subunit
Similarity search - Component
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.36 Å
AuthorsFang CL / Gouaux E
Funding support United States, 1 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: To Be Published
Title: Native AMPA receptor architecture reveals SynDIG4 engagement and auxiliary subunit heterogeneity
Authors: Fang CL / Gouaux E
History
DepositionDec 7, 2025-
Header (metadata) releaseApr 29, 2026-
Map releaseApr 29, 2026-
UpdateApr 29, 2026-
Current statusApr 29, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_74381.png

Downloads & links

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Map

FileDownload / File: emd_74381.map.gz / Format: CCP4 / Size: 229.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 392 pix.
= 323.4 Å		0.83 Å/pix.
x 392 pix.
= 323.4 Å		0.83 Å/pix.
x 392 pix.
= 323.4 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.825 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.086
Minimum - Maximum-0.55735266 - 0.8327768
Average (Standard dev.)0.00026165438 (±0.018733917)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions392392392
Spacing392392392
CellA=B=C: 323.4 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: #1

Fileemd_74381_additional_1.map
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Half map: #1

Fileemd_74381_half_map_1.map
Projections & Slices
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Half map: #2

Fileemd_74381_half_map_2.map
Projections & Slices
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Histogram (log scale)

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Sample components

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Entire : native mouse AMPAR

EntireName: native mouse AMPAR
Components
  • Complex: native mouse AMPAR
    • Protein or peptide: Glutamate receptor 1
    • Protein or peptide: Glutamate receptor 2
    • Protein or peptide: Protein cornichon homolog 2
    • Protein or peptide: Voltage-dependent calcium channel gamma-2 subunit
    • Protein or peptide: Voltage-dependent calcium channel gamma-8 subunit
  • Ligand: PALMITIC ACID
  • Ligand: (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate

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Supramolecule #1: native mouse AMPAR

SupramoleculeName: native mouse AMPAR / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: Glutamate receptor 1

MacromoleculeName: Glutamate receptor 1 / type: protein_or_peptide / ID: 1 / Details: Mix of AMPAR subunits (GluA1, GluA3, and GluA4) / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 55.260184 KDa
SequenceString: TYIVTTILED PYVMLKKNAN QFEGNDRYEG YCVELAAEIA KHVGYSYRLE IVSDGKYGAR DPDTKAWNGM VGELVYGRAD VAVAPLTIT LVREEVIDFS KPFMSLGISI MIKKPQKSKP GVFSFLDPLA YEIWMCIVFA YIGVSVVLFL VSRFSPYEWH S EEFEEGRD ...String:
TYIVTTILED PYVMLKKNAN QFEGNDRYEG YCVELAAEIA KHVGYSYRLE IVSDGKYGAR DPDTKAWNGM VGELVYGRAD VAVAPLTIT LVREEVIDFS KPFMSLGISI MIKKPQKSKP GVFSFLDPLA YEIWMCIVFA YIGVSVVLFL VSRFSPYEWH S EEFEEGRD QTTSDQSNEF GIFNSLWFSL GAFMQQGCDI SPRSLSGRIV GGVWWFFTLI IISSYTANLA AFLTVERMVS PI ESAEDLA KQTEIAYGTL EAGSTKEFFR RSKIAVFEKM WTYMKSAEPS VFVRTTEEGM IRVRKSKGKY AYLLESTMNE YIE QRKPCD TMKVGGNLDS KGYGIATPKG SALRGPVNLA VLKLSEQGVL DKLKSKWWYD KGECGSKDSG SKDKTSALSL SNVA GVFYI LIGGLGLAML VALIEFCYKS RSESKRMKGF CLIPQQSINE AIRTSTLPRN SGAGASGGSG SGENGRVVSQ DFPKS MQSI PCMSHSSGMP LGATGL

UniProtKB: Glutamate receptor 1

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Macromolecule #2: Glutamate receptor 2

MacromoleculeName: Glutamate receptor 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 52.118758 KDa
SequenceString: VVTTILESPY VMMKKNHEML EGNERYEGYC VDLAAEIAKH CGFKYKLTIV GDGKYGARDA DTKIWNGMVG ELVYGKADIA IAPLTITLV REEVIDFSKP FMSLGISIMI KKPQKSKPGV FSFLDPLAYE IWMCIVFAYI GVSVVLFLVS RFSPYEWHTE E FEDGRETQ ...String:
VVTTILESPY VMMKKNHEML EGNERYEGYC VDLAAEIAKH CGFKYKLTIV GDGKYGARDA DTKIWNGMVG ELVYGKADIA IAPLTITLV REEVIDFSKP FMSLGISIMI KKPQKSKPGV FSFLDPLAYE IWMCIVFAYI GVSVVLFLVS RFSPYEWHTE E FEDGRETQ SSESTNEFGI FNSLWFSLGA FMRQGCDISP RSLSGRIVGG VWWFFTLIII SSYTANLAAF LTVERMVSPI ES AEDLSKQ TEIAYGTLDS GSTKEFFRRS KIAVFDKMWT YMRSAEPSVF VRTTAEGVAR VRKSKGKYAY LLESTMNEYI EQR KPCDTM KVGGNLDSKG YGIATPKGSS LRNAVNLAVL KLNEQGLLDK LKNKWWYDKG ECGSGGGDSK EKTSALSLSN VAGV FYILV GGLGLAMLVA LIEFCYKSRA EAKRMKVAKN AQNINPSSSQ NSQNFATYKE GYNVYGIESV KI

UniProtKB: Glutamate receptor

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Macromolecule #3: Protein cornichon homolog 2

MacromoleculeName: Protein cornichon homolog 2 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 18.94842 KDa
SequenceString:
MAFTFAAFCY MLTLVLCASL IFFVIWHIIA FDELRTDFKN PIDQGNPARA RERLKNIERI CCLLRKLVVP EYSIHGLFCL MFLCAAEWV TLGLNIPLLF YHLWRYFHRP ADGSEVMYDA VSIMNADILN YCQKESWCKL AFYLLSFFYY LYSMVYTLVS F

UniProtKB: Protein cornichon homolog 2

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Macromolecule #4: Voltage-dependent calcium channel gamma-2 subunit

MacromoleculeName: Voltage-dependent calcium channel gamma-2 subunit / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 35.938746 KDa
SequenceString: MGLFDRGVQM LLTTVGAFAA FSLMTIAVGT DYWLYSRGVC KTKSVSENET SKKNEEVMTH SGLWRTCCLE GNFKGLCKQI DHFPEDADY EADTAEYFLR AVRASSIFPI LSVILLFMGG LCIAASEFYK TRHNIILSAG IFFVSAGLSN IIGIIVYISA N AGDPSKSD ...String:
MGLFDRGVQM LLTTVGAFAA FSLMTIAVGT DYWLYSRGVC KTKSVSENET SKKNEEVMTH SGLWRTCCLE GNFKGLCKQI DHFPEDADY EADTAEYFLR AVRASSIFPI LSVILLFMGG LCIAASEFYK TRHNIILSAG IFFVSAGLSN IIGIIVYISA N AGDPSKSD SKKNSYSYGW SFYFGALSFI IAEMVGVLAV HMFIDRHKQL RATARATDYL QASAITRIPS YRYRYQRRSR SS SRSTEPS HSRDASPVGV KGFNTLPSTE ISMYTLSRDP LKAATTPTAT YNSDRDNSFL QVHNCIQKDS KDSLHANTAN RRT TPV

UniProtKB: Voltage-dependent calcium channel gamma-2 subunit

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Macromolecule #5: Voltage-dependent calcium channel gamma-8 subunit

MacromoleculeName: Voltage-dependent calcium channel gamma-8 subunit / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 43.502938 KDa
SequenceString: MESLKRWNEE RGLWCEKGVQ VLLTTIGAFS AFGLMTIAIS TDYWLYTRAL ICNTTNLTAG DDGPPHRGGS GSSEKKDPGG LTHSGLWRI CCLEGLKRGV CVKINHFPED TDYDHDSAEY LLRVVRASSI FPILSAILLL LGGVCVAASR VYKSKRNIIL G AGILFVAA ...String:
MESLKRWNEE RGLWCEKGVQ VLLTTIGAFS AFGLMTIAIS TDYWLYTRAL ICNTTNLTAG DDGPPHRGGS GSSEKKDPGG LTHSGLWRI CCLEGLKRGV CVKINHFPED TDYDHDSAEY LLRVVRASSI FPILSAILLL LGGVCVAASR VYKSKRNIIL G AGILFVAA GLSNIIGVIV YISANAGEPG PKRDEEKKNH YSYGWSFYFG GLSFILAEVI GVLAVNIYIE RSREAHCQSR SD LLKAGGG AGGSGGSGPS AILRLPSYRF RYRRRSRSSS RGSSEASPSR DASPGGPGGP GFASTDISMY TLSRDPSKGS VAA GLASAG GGGSGAGVGA YGGAAGAAGG GGAGSERDRG SSAGFLTLHN AFPKEAASGV TVTVTGPPAA PAPAPAPPAP AAPA PGTLS KEAAASNTNT LNRKTTPV

UniProtKB: Voltage-dependent calcium channel gamma-8 subunit

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Macromolecule #6: PALMITIC ACID

MacromoleculeName: PALMITIC ACID / type: ligand / ID: 6 / Number of copies: 10 / Formula: PLM
Molecular weightTheoretical: 256.424 Da
Chemical component information

ChemComp-PLM:
PALMITIC ACID

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Macromolecule #7: (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate

MacromoleculeName: (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / type: ligand / ID: 7 / Number of copies: 8 / Formula: OLC
Molecular weightTheoretical: 356.54 Da
Chemical component information

ChemComp-OLC:
(2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate

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Macromolecule #8: (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: 8 / Number of copies: 6 / 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

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: OTHER / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.36 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 45742
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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