+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4575 | |||||||||
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Title | Full length GluA1/2-gamma8 complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information Phase 2 - plateau phase / Phase 0 - rapid depolarisation / Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex ...Phase 2 - plateau phase / Phase 0 - rapid depolarisation / Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex / LGI-ADAM interactions / myosin V binding / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Trafficking of AMPA receptors / neuron spine / regulation of AMPA receptor activity / protein phosphatase 2B binding / neurotransmitter receptor internalization / response to arsenic-containing substance / cellular response to dsRNA / postsynaptic neurotransmitter receptor diffusion trapping / dendritic spine membrane / Synaptic adhesion-like molecules / long-term synaptic depression / beta-2 adrenergic receptor binding / cellular response to peptide hormone stimulus / protein kinase A binding / spinal cord development / spine synapse / dendritic spine neck / neuronal cell body membrane / dendritic spine head / Activation of AMPA receptors / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / channel regulator activity / ligand-gated monoatomic cation channel activity / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / regulation of postsynaptic membrane neurotransmitter receptor levels / immunoglobulin binding / AMPA glutamate receptor complex / adenylate cyclase binding / kainate selective glutamate receptor activity / cellular response to organic cyclic compound / ionotropic glutamate receptor complex / excitatory synapse / extracellularly glutamate-gated ion channel activity / neuronal action potential / cellular response to glycine / calcium channel regulator activity / asymmetric synapse / G-protein alpha-subunit binding / regulation of receptor recycling / voltage-gated calcium channel activity / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / postsynaptic density, intracellular component / positive regulation of synaptic transmission / glutamate receptor binding / long-term memory / extracellular ligand-gated monoatomic ion channel activity / positive regulation of synaptic transmission, glutamatergic / response to electrical stimulus / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / response to fungicide / regulation of synaptic transmission, glutamatergic / somatodendritic compartment / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / cytoskeletal protein binding / ionotropic glutamate receptor binding / dendrite cytoplasm / ionotropic glutamate receptor signaling pathway / cellular response to amino acid stimulus / SNARE binding / response to cocaine / dendritic shaft / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / long-term synaptic potentiation / protein tetramerization / postsynaptic density membrane / modulation of chemical synaptic transmission / establishment of protein localization / neuromuscular junction / regulation of synaptic plasticity / Schaffer collateral - CA1 synapse / terminal bouton / response to organic cyclic compound / recycling endosome / receptor internalization / response to toxic substance Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.3 Å | |||||||||
Authors | Herguedas B / Garcia-Nafria J / Greger IG | |||||||||
Citation | Journal: Science / Year: 2019 Title: Architecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP γ8. Authors: Beatriz Herguedas / Jake F Watson / Hinze Ho / Ondrej Cais / Javier García-Nafría / Ingo H Greger / Abstract: AMPA-type glutamate receptors (AMPARs) mediate excitatory neurotransmission and are central regulators of synaptic plasticity, a molecular mechanism underlying learning and memory. Although AMPARs ...AMPA-type glutamate receptors (AMPARs) mediate excitatory neurotransmission and are central regulators of synaptic plasticity, a molecular mechanism underlying learning and memory. Although AMPARs act predominantly as heteromers, structural studies have focused on homomeric assemblies. Here, we present a cryo-electron microscopy structure of the heteromeric GluA1/2 receptor associated with two transmembrane AMPAR regulatory protein (TARP) γ8 auxiliary subunits, the principal AMPAR complex at hippocampal synapses. Within the receptor, the core subunits arrange to give the GluA2 subunit dominant control of gating. This structure reveals the geometry of the Q/R site that controls calcium flux, suggests association of TARP-stabilized lipids, and demonstrates that the extracellular loop of γ8 modulates gating by selectively interacting with the GluA2 ligand-binding domain. Collectively, this structure provides a blueprint for deciphering the signal transduction mechanisms of synaptic AMPARs. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4575.map.gz | 6.6 MB | EMDB map data format | |
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Header (meta data) | emd-4575-v30.xml emd-4575.xml | 18.1 KB 18.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_4575_fsc.xml | 9.2 KB | Display | FSC data file |
Images | emd_4575.png | 65.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4575 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4575 | HTTPS FTP |
-Validation report
Summary document | emd_4575_validation.pdf.gz | 247.4 KB | Display | EMDB validaton report |
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Full document | emd_4575_full_validation.pdf.gz | 246.6 KB | Display | |
Data in XML | emd_4575_validation.xml.gz | 9.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4575 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4575 | HTTPS FTP |
-Related structure data
Related structure data | 6qkzMC 4572C 6qkcC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4575.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.4 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : GluA1/A2 bound to gamma-8
Entire | Name: GluA1/A2 bound to gamma-8 |
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Components |
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-Supramolecule #1: GluA1/A2 bound to gamma-8
Supramolecule | Name: GluA1/A2 bound to gamma-8 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Recombinant expression | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 447 kDa/nm |
-Macromolecule #1: GluA1
Macromolecule | Name: GluA1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 100.739602 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ADYKDDDDKN FPNNIQIGGL FPNQQSQEHA AFRFALSQLT EPPKLLPQID IVNISDSFEM TYRFCSQFSK GVYAIFGFYE RRTVNMLTS FCGALHVCFI TPSFPVDTSN QFVLQLRPEL QEALISIIDH YKWQTFVYIY DADRGLSVLQ RVLDTAAEKN W QVTAVNIL ...String: ADYKDDDDKN FPNNIQIGGL FPNQQSQEHA AFRFALSQLT EPPKLLPQID IVNISDSFEM TYRFCSQFSK GVYAIFGFYE RRTVNMLTS FCGALHVCFI TPSFPVDTSN QFVLQLRPEL QEALISIIDH YKWQTFVYIY DADRGLSVLQ RVLDTAAEKN W QVTAVNIL TTTEEGYRML FQDLEKKKER LVVVDCESER LNAILGQIVK LEKNGIGYHY ILANLGFMDI DLNKFKESGA NV TGFQLVN YTDTIPARIM QQWRTSDSRD HTRVDWKRPK YTSALTYDGV KVMAEAFQSL RRQRIDISRR GNAGDCLANP AVP WGQGID IQRALQQVRF EGLTGNVQFN EKGRRTNYTL HVIEMKHDGI RKIGYWNEDD KFVPAATDAQ AGGDNSSVQN RTYI VTTIL EDPYVMLKKN ANQFEGNDRY EGYCVELAAE IAKHVGYSYR LEIVSDGKYG ARDPDTKAWN GMVGELVYGR ADVAV APLT ITLVREEVID FSKPFMSLGI SIMIKKPQKS KPGVFSFLDP LAYEIWMCIV FAYIGVSVVL FLVSRFSPYE WHSEEF EEG RDQTTSDQSN EFGIFNSLWF SLGAFMQQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VSPIESA ED LAKQTEIAYG TLEAGSTKEF FRRSKIAVFE KMWTYMKSAE PSVFVRTTEE GMIRVRKSKG KYAYLLESTM NEYIEQRK P CDTMKVGGNL DSKGYGIATP KGSALRGPVN LAVLKLSEQG VLDKLKSKWW YDKGECGSKD SGSKDKTSAL SLSNVAGVF YILIGGLGLA MLVALIEFCY KSRSESKRMK GFCLIPQQSI NEAIRTSTLP RNSGAGASGG GGSGENGRVV SQDFPKSMQS IPCMSHSSG MPLGATGL |
-Macromolecule #2: Glutamate receptor 2
Macromolecule | Name: Glutamate receptor 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 93.880078 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VSSNSIQIGG LFPRGADQEY SAFRVGMVQF STSEFRLTPH IDNLEVANSF AVTNAFCSQF SRGVYAIFGF YDKKSVNTIT SFCGTLHVS FITPSFPTDG THPFVIQMRP DLKGALLSLI EYYQWDKFAY LYDSDRGLST LQAVLDSAAE KKWQVTAINV G NINNDKKD ...String: VSSNSIQIGG LFPRGADQEY SAFRVGMVQF STSEFRLTPH IDNLEVANSF AVTNAFCSQF SRGVYAIFGF YDKKSVNTIT SFCGTLHVS FITPSFPTDG THPFVIQMRP DLKGALLSLI EYYQWDKFAY LYDSDRGLST LQAVLDSAAE KKWQVTAINV G NINNDKKD ETYRSLFQDL ELKKERRVIL DCERDKVNDI VDQVITIGKH VKGYHYIIAN LGFTDGDLLK IQFGGANVSG FQ IVDYDDS LVSKFIERWS TLEEKEYPGA HTATIKYTSA LTYDAVQVMT EAFRNLRKQR IEISRRGNAG DCLANPAVPW GQG VEIERA LKQVQVEGLS GNIKFDQNGK RINYTINIME LKTNGPRKIG YWSEVDKMVV TLTELPSGND TSGLENKTVV VTTI LESPY VMMKKNHEML EGNERYEGYC VDLAAEIAKH CGFKYKLTIV GDGKYGARDA DTKIWNGMVG ELVYGKADIA IAPLT ITLV REEVIDFSKP FMSLGISIMI KKPQKSKPGV FSFLDPLAYE IWMCIVFAYI GVSVVLFLVS RFSPYEWHTE EFEDGR ETQ SSESTNEFGI FNSLWFSLGA FMRQGCDISP RSLSGRIVGG VWWFFTLIII SSYTANLAAF LTVERMVSPI ESAEDLS KQ TEIAYGTLDS GSTKEFFRRS KIAVFDKMWT YMRSAEPSVF VRTTAEGVAR VRKSKGKYAY LLESTMNEYI EQRKPCDT M KVGGNLDSKG YGIATPKGSS LGTPVNLAVL KLSEQGVLDK LKNKWWYDKG ECGAKDSGSK EKTSALSLSN VAGVFYILV GGLGLAMLVA LIEFCYKSRA EAKRMKVAKN PQNINPSSS |
-Macromolecule #3: Voltage-dependent calcium channel gamma-8 subunit
Macromolecule | Name: Voltage-dependent calcium channel gamma-8 subunit / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 43.592008 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GESLKRWNEE RGLWCEKGVQ VLLTTIGAFA AFGLMTIAIS TDYWLYTRAL ICNTTNLTAG DDGPPHRGGS GSSEKKDPGG LTHSGLWRI CCLEGLKRGV CVKINHFPED TDYDHDSSEY LLRVVRASSI FPILSAILLL LGGVCVAASR VYKSKRNIIL G AGILFVAA ...String: GESLKRWNEE RGLWCEKGVQ VLLTTIGAFA AFGLMTIAIS TDYWLYTRAL ICNTTNLTAG DDGPPHRGGS GSSEKKDPGG LTHSGLWRI CCLEGLKRGV CVKINHFPED TDYDHDSSEY LLRVVRASSI FPILSAILLL LGGVCVAASR VYKSKRNIIL G AGILFVAA GLSNIIGVIV YISANAGEPG PKRDEEKKNH YSYGWSFYFG GLSFILAEVI GVLAVNIYIE RSREAHCQSR SD LLKAGGG AGGSGGSGPS AILRLPSYRF RYRRRSRSSS RGSSEASPSR DASPGGPGGP GFASTDISMY TLSRDPSKGS VAA GLASAG GGGGGAGVGA YGGAAGAAGG GGTGSERDRG SSAGFLTLHN AFPKEAASGV TVTVTGPPAA PAPAPPAPAA PAPG TLSKE AAASNTNTLN RKLEVLFQ |
-Macromolecule #6: 6-nitro-2,3-bis(oxidanylidene)-1,4-dihydrobenzo[f]quinoxaline-7-s...
Macromolecule | Name: 6-nitro-2,3-bis(oxidanylidene)-1,4-dihydrobenzo[f]quinoxaline-7-sulfonamide type: ligand / ID: 6 / Number of copies: 4 / Formula: E2Q |
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Molecular weight | Theoretical: 336.28 Da |
Chemical component information | ChemComp-E2Q: |
-Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.4 mg/mL |
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Buffer | pH: 8 Details: 25 mM TRIS, pH 8, 150 mM NaCl and 0.1 % digitonin (w/v) |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV Details: 3uL on grid, 60 sec incubation and 4sec blotting time. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 100.0 K / Max: 100.0 K |
Specialist optics | Phase plate: VOLTA PHASE PLATE / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Number grids imaged: 3 / Number real images: 5005 / Average exposure time: 14.0 sec. / Average electron dose: 32.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: -0.9 µm / Nominal defocus min: -0.2 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |