[English] 日本語
Yorodumi
- EMDB-23292: The composite LBD-TMD structure combined from all hippocampal AMP... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-23292
TitleThe composite LBD-TMD structure combined from all hippocampal AMPAR subtypes at 3.25 Angstrom resolution
Map data
Sample
  • Complex: Composite LBD-TMD complex from the combined hippocampal AMPAR subtypes
    • Protein or peptide: x 5 types
  • Ligand: x 7 types
Function / homology
Function and homology information


Phase 2 - plateau phase / Phase 0 - rapid depolarisation / negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Cargo concentration in the ER / LGI-ADAM interactions / COPII-mediated vesicle transport / Trafficking of AMPA receptors / localization within membrane / neurotransmitter receptor transport, postsynaptic endosome to lysosome ...Phase 2 - plateau phase / Phase 0 - rapid depolarisation / negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Cargo concentration in the ER / LGI-ADAM interactions / COPII-mediated vesicle transport / Trafficking of AMPA receptors / localization within membrane / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / protein phosphatase 2B binding / postsynaptic neurotransmitter receptor diffusion trapping / transmission of nerve impulse / regulation of postsynaptic membrane neurotransmitter receptor levels / calcium channel regulator activity / AMPA glutamate receptor complex / voltage-gated calcium channel activity / glutamate-gated receptor activity / vesicle-mediated transport / dendrite membrane / ionotropic glutamate receptor binding / regulation of membrane potential / positive regulation of synaptic transmission, glutamatergic / dendritic shaft / synaptic transmission, glutamatergic / postsynaptic density membrane / Schaffer collateral - CA1 synapse / postsynaptic membrane / dendritic spine / postsynaptic density / membrane => GO:0016020 / dendrite / synapse / glutamatergic synapse / endoplasmic reticulum membrane
Similarity search - Function
Voltage-dependent calcium channel, gamma-8 subunit / Cornichon / Cornichon, conserved site / Cornichon protein / Cornichon family signature. / Cornichon / PMP-22/EMP/MP20/Claudin family / Voltage-dependent calcium channel, gamma subunit / PMP-22/EMP/MP20/Claudin superfamily / Ionotropic glutamate receptor, metazoa ...Voltage-dependent calcium channel, gamma-8 subunit / Cornichon / Cornichon, conserved site / Cornichon protein / Cornichon family signature. / Cornichon / 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-8 subunit
Similarity search - Component
Biological speciesMus musculus (house mouse) / Mouse (mice)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.25 Å
AuthorsYu J / Rao P / Gouaux E
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS038631 United States
CitationJournal: Nature / Year: 2021
Title: Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition.
Authors: Jie Yu / Prashant Rao / Sarah Clark / Jaba Mitra / Taekjip Ha / Eric Gouaux /
Abstract: AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus. The trafficking, localization, kinetics and pharmacology of AMPA receptors are ...AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus. The trafficking, localization, kinetics and pharmacology of AMPA receptors are tuned by an ensemble of auxiliary protein subunits, which are integral membrane proteins that associate with the receptor to yield bona fide receptor signalling complexes. Thus far, extensive studies of recombinant AMPA receptor-auxiliary subunit complexes using engineered protein constructs have not been able to faithfully elucidate the molecular architecture of hippocampal AMPA receptor complexes. Here we obtain mouse hippocampal, calcium-impermeable AMPA receptor complexes using immunoaffinity purification and use single-molecule fluorescence and cryo-electron microscopy experiments to elucidate three major AMPA receptor-auxiliary subunit complexes. The GluA1-GluA2, GluA1-GluA2-GluA3 and GluA2-GluA3 receptors are the predominant assemblies, with the auxiliary subunits TARP-γ8 and CNIH2-SynDIG4 non-stochastically positioned at the B'/D' and A'/C' positions, respectively. We further demonstrate how the receptor-TARP-γ8 stoichiometry explains the mechanism of and submaximal inhibition by a clinically relevant, brain-region-specific allosteric inhibitor.
History
DepositionJan 14, 2021-
Header (metadata) releaseMay 12, 2021-
Map releaseMay 12, 2021-
UpdateJun 30, 2021-
Current statusJun 30, 2021Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.16
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.16
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7lep
  • Surface level: 0.16
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_23292.png

Downloads & links

-
Map

FileDownload / File: emd_23292.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.1035 Å
Density
Contour LevelBy AUTHOR: 0.156 / Movie #1: 0.16
Minimum - Maximum-0.78660184 - 1.1914166
Average (Standard dev.)-0.0003990681 (±0.02026142)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 441.4 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.10351.10351.1035
M x/y/z400400400
origin x/y/z0.0000.0000.000
length x/y/z441.400441.400441.400
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS400400400
D min/max/mean-0.7871.191-0.000

-
Supplemental data

-
Sample components

+
Entire : Composite LBD-TMD complex from the combined hippocampal AMPAR subtypes

EntireName: Composite LBD-TMD complex from the combined hippocampal AMPAR subtypes
Components
  • Complex: Composite LBD-TMD complex from the combined hippocampal AMPAR subtypes
    • Protein or peptide: Mix of AMPAR subunits (GluA1, GluA3, and GluA4)
    • Protein or peptide: Glutamate receptor 2GRIA2
    • Protein or peptide: Mix of AMPAR subunits (GluA1, GluA3, and GluAX)
    • Protein or peptide: Protein cornichon homolog 2
    • Protein or peptide: Voltage-dependent calcium channel gamma-8 subunit
  • Ligand: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
  • Ligand: TETRADECANE
  • Ligand: DECANE
  • Ligand: 6-[2-chloro-6-(trifluoromethoxy)phenyl]-1H-benzimidazol-2-ol
  • Ligand: N-OCTANEOctane
  • Ligand: DODECANE

+
Supramolecule #1: Composite LBD-TMD complex from the combined hippocampal AMPAR subtypes

SupramoleculeName: Composite LBD-TMD complex from the combined hippocampal AMPAR subtypes
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 / Details: Bound with MPQX and JNJ55511118
Source (natural)Organism: Mus musculus (house mouse)

+
Macromolecule #1: Mix of AMPAR subunits (GluA1, GluA3, and GluA4)

MacromoleculeName: Mix of AMPAR subunits (GluA1, GluA3, and GluA4) / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mouse (mice)
Molecular weightTheoretical: 43.650676 KDa
SequenceString: TAAVTTIAEA PYVMLKKNAA AAEGNAAYEG YCVALAAEIA KHAGAAYAAA IVADGKYGAR DAATKAWNGM VGELVYGRAA AAAAPLTIT LVREEVIDFS KPFMSLGISI MIKKPQKSKP GVFSFLDPLA YEIWMCIVFA YIGVSVVLFL VSRFS(UNK) (UNK)(UNK)(UNK) ...String:
TAAVTTIAEA PYVMLKKNAA AAEGNAAYEG YCVALAAEIA KHAGAAYAAA IVADGKYGAR DAATKAWNGM VGELVYGRAA AAAAPLTIT LVREEVIDFS KPFMSLGISI MIKKPQKSKP GVFSFLDPLA YEIWMCIVFA YIGVSVVLFL VSRFS(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)NEF GIFNSLWFSL GAFMQQGCDI SPRSLSG RI VGGVWWFFTL IIISSYTANL AAFLTVERMV SPIESAEDLA KQTEIAYGTL AAGSTKEFFR RSKIAVAAKM WAYMASAE P SVFAATTAAG AARVRKAKGK AAALLESTMN EYIEQRKPCD TMKVGGNLDS KGYGAATPKG SALRAPVNLA VLKLAEQGA LDKLKNKWWY DKGECGAAAA ASKAKTSALS LSNVAGVFYI LAGGLGLAMA VALIEFCYK

+
Macromolecule #2: Glutamate receptor 2

MacromoleculeName: Glutamate receptor 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mouse (mice)
Molecular weightTheoretical: 47.252312 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 LGNAVNLAVL KLNEEGLLDK LKNKWWYDKG ECGSGGGDSK EKTSALSLSN VAGV FYILV GGLGLAMLVA LIEFCYKSR

+
Macromolecule #3: Mix of AMPAR subunits (GluA1, GluA3, and GluAX)

MacromoleculeName: Mix of AMPAR subunits (GluA1, GluA3, and GluAX) / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mouse (mice)
Molecular weightTheoretical: 43.702637 KDa
SequenceString: TAVVTTILED PYVMAKKNAA AAEGNAAYEG YCVALAAEIA KHAAYAYAAA IVADGKYGAR DAATKAWNGM VGELVYGAAD AAAAPLTIT LVREEVIDFS KPFMSLGISI MIKKPQKSKP GVFSFLDPLA YEIWMCIVFA YIGVSVVLFL VSRFS(UNK) (UNK)(UNK)(UNK) ...String:
TAVVTTILED PYVMAKKNAA AAEGNAAYEG YCVALAAEIA KHAAYAYAAA IVADGKYGAR DAATKAWNGM VGELVYGAAD AAAAPLTIT LVREEVIDFS KPFMSLGISI MIKKPQKSKP GVFSFLDPLA YEIWMCIVFA YIGVSVVLFL VSRFS(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)NEFG IFNSLWFSLG AFMQQGCDIS PRSLSGRIVG G VWWFFTLI IISSYTANLA AFLTVERMVS PIESAEDLAK QTEIAYGTLA AGSTKEFFRR SKIAVAAKMW AYMASAEPSV FA ATTAAGA ARVRKAKGKA AALLESTMNE YIEQRKPCDT MKVGGNLDSK GYGAATPKGS ALRAPVNLAV LKLAEQGALD KLK AKWWYD KGECGAAAAA SKDKTSALSL SNVAGVFYIL AGGLGLAMAV ALIEFCYK

+
Macromolecule #4: Protein cornichon homolog 2

MacromoleculeName: Protein cornichon homolog 2 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mouse (mice)
Molecular weightTheoretical: 18.755152 KDa
SequenceString:
AFTFAAFCYM LTLVLCASLI FFVIWHIIAF DELRTDFKNP IDQGNPARAR ERLKNIERIC CLLRKLVVPE YSIHGLFCLM FLCAAEWVT LGLNIPLLFT HLWRYFHRPA DGSEVMYDAV SIMNADILNY CQKESWCKLA FYLLSFFYYL YSMVYTLVSF

+
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: Mouse (mice)
Molecular weightTheoretical: 23.242705 KDa
SequenceString: VQVLLTTIGA FSAFGLMTIA ISTDYWLYTR ALICNTTNLT AGDDGPPHRG GSGSSEKKDP GGLTHSGLWR ICCLEGLKRG VCVKINHFP EDTDYDHDSA EYLLRVVRAS SIFPILSAIL LLLGGVCVAA SRVYKSKRNI ILGAGILFVA AGLSNIIGVI V YISANAGE ...String:
VQVLLTTIGA FSAFGLMTIA ISTDYWLYTR ALICNTTNLT AGDDGPPHRG GSGSSEKKDP GGLTHSGLWR ICCLEGLKRG VCVKINHFP EDTDYDHDSA EYLLRVVRAS SIFPILSAIL LLLGGVCVAA SRVYKSKRNI ILGAGILFVA AGLSNIIGVI V YISANAGE PGPKRDEEKK NHYSYGWSFY FGGLSFILAE VIGVLAVNIY IERSREA

+
Macromolecule #6: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquino...

MacromoleculeName: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid
type: ligand / ID: 6 / Number of copies: 4 / Formula: ZK1
Molecular weightTheoretical: 409.254 Da
Chemical component information

ChemComp-ZK1:
{[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid / antagonist, medication*YM / Fanapanel

+
Macromolecule #7: (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: 7 / Number of copies: 30 / 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 / POPC

+
Macromolecule #8: TETRADECANE

MacromoleculeName: TETRADECANE / type: ligand / ID: 8 / Number of copies: 1 / Formula: C14
Molecular weightTheoretical: 198.388 Da
Chemical component information

ChemComp-C14:
TETRADECANE / Tetradecane

+
Macromolecule #9: DECANE

MacromoleculeName: DECANE / type: ligand / ID: 9 / Number of copies: 1 / Formula: D10
Molecular weightTheoretical: 142.282 Da
Chemical component information

ChemComp-D10:
DECANE / Decane

+
Macromolecule #10: 6-[2-chloro-6-(trifluoromethoxy)phenyl]-1H-benzimidazol-2-ol

MacromoleculeName: 6-[2-chloro-6-(trifluoromethoxy)phenyl]-1H-benzimidazol-2-ol
type: ligand / ID: 10 / Number of copies: 2 / Formula: XVD
Molecular weightTheoretical: 328.674 Da
Chemical component information

ChemComp-XVD:
6-[2-chloro-6-(trifluoromethoxy)phenyl]-1H-benzimidazol-2-ol

+
Macromolecule #11: N-OCTANE

MacromoleculeName: N-OCTANE / type: ligand / ID: 11 / Number of copies: 2 / Formula: OCT
Molecular weightTheoretical: 114.229 Da
Chemical component information

ChemComp-OCT:
N-OCTANE / Octane

+
Macromolecule #12: DODECANE

MacromoleculeName: DODECANE / type: ligand / ID: 12 / Number of copies: 2 / Formula: D12
Molecular weightTheoretical: 170.335 Da
Chemical component information

ChemComp-D12:
DODECANE / Dodecane

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

CTF correctionSoftware - Name: cryoSPARC
Startup modelType of model: INSILICO MODEL
In silico model: The LBD-TMD GluA1/GluA2 hippocampal AMPAR complex
Details: We used the LBD-TMD GluA1/GluA2 model as the initial template.
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.25 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 116710

+
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