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Yorodumi- EMDB-16381: Resting state homomeric GluA2 F231A mutant AMPA receptor in compl... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16381 | |||||||||
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Title | Resting state homomeric GluA2 F231A mutant AMPA receptor in complex with TARP gamma-2 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | AMPAR / ion channels / neurotransmission / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information Presynaptic depolarization and calcium channel opening / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / LGI-ADAM interactions / Trafficking of AMPA receptors / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity ...Presynaptic depolarization and calcium channel opening / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / LGI-ADAM interactions / Trafficking of AMPA receptors / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / membrane hyperpolarization / postsynaptic neurotransmitter receptor diffusion trapping / nervous system process / protein targeting to membrane / neurotransmitter receptor localization to postsynaptic specialization membrane / voltage-gated calcium channel complex / neuromuscular junction development / spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / regulation of postsynaptic membrane neurotransmitter receptor levels / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / immunoglobulin binding / membrane depolarization / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / cellular response to glycine / calcium channel regulator activity / asymmetric synapse / regulation of receptor recycling / voltage-gated calcium channel activity / Unblocking of NMDA receptors, glutamate binding and activation / glutamate receptor binding / positive regulation of synaptic transmission / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / regulation of synaptic transmission, glutamatergic / somatodendritic compartment / 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 signaling pathway / dendrite cytoplasm / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / SNARE binding / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / regulation of membrane potential / protein tetramerization / postsynaptic density membrane / ionotropic glutamate receptor binding / Schaffer collateral - CA1 synapse / modulation of chemical synaptic transmission / establishment of protein localization / terminal bouton / receptor internalization / cerebral cortex development / synaptic vesicle membrane / response to calcium ion / synaptic vesicle / presynapse / presynaptic membrane / signaling receptor activity / amyloid-beta binding / growth cone / scaffold protein binding / chemical synaptic transmission / postsynaptic membrane / perikaryon / dendritic spine / postsynaptic density / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / dendrite / protein-containing complex binding / endoplasmic reticulum membrane / protein kinase binding / cell surface / endoplasmic reticulum / protein-containing complex / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus (rat) / Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Zhang D / Ivica J / Krieger JM / Ho H / Yamashita K / Cais O / Greger I | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Nature / Year: 2023 Title: Structural mobility tunes signalling of the GluA1 AMPA glutamate receptor. Authors: Danyang Zhang / Josip Ivica / James M Krieger / Hinze Ho / Keitaro Yamashita / Imogen Stockwell / Rozbeh Baradaran / Ondrej Cais / Ingo H Greger / Abstract: AMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca-impermeable, or GluA2-lacking and Ca-permeable. ...AMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca-impermeable, or GluA2-lacking and Ca-permeable. Despite their prominent expression throughout interneurons and glia, their role in long-term potentiation and their involvement in a range of neuropathologies, structural information for GluA2-lacking receptors is currently absent. Here we determine and characterize cryo-electron microscopy structures of the GluA1 homotetramer, fully occupied with TARPγ3 auxiliary subunits (GluA1/γ3). The gating core of both resting and open-state GluA1/γ3 closely resembles GluA2-containing receptors. However, the sequence-diverse N-terminal domains (NTDs) give rise to a highly mobile assembly, enabling domain swapping and subunit re-alignments in the ligand-binding domain tier that are pronounced in desensitized states. These transitions underlie the unique kinetic properties of GluA1. A GluA2 mutant (F231A) increasing NTD dynamics phenocopies this behaviour, and exhibits reduced synaptic responses, reflecting the anchoring function of the AMPAR NTD at the synapse. Together, this work underscores how the subunit-diverse NTDs determine subunit arrangement, gating properties and ultimately synaptic signalling efficiency among AMPAR subtypes. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16381.map.gz | 19.5 MB | EMDB map data format | |
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Header (meta data) | emd-16381-v30.xml emd-16381.xml | 18 KB 18 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16381_fsc.xml | 15.9 KB | Display | FSC data file |
Images | emd_16381.png | 86.2 KB | ||
Masks | emd_16381_msk_1.map | 127.4 MB | Mask map | |
Filedesc metadata | emd-16381.cif.gz | 6.7 KB | ||
Others | emd_16381_half_map_1.map.gz emd_16381_half_map_2.map.gz | 117 MB 117 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16381 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16381 | HTTPS FTP |
-Validation report
Summary document | emd_16381_validation.pdf.gz | 955.9 KB | Display | EMDB validaton report |
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Full document | emd_16381_full_validation.pdf.gz | 955.5 KB | Display | |
Data in XML | emd_16381_validation.xml.gz | 20.7 KB | Display | |
Data in CIF | emd_16381_validation.cif.gz | 27 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16381 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16381 | HTTPS FTP |
-Related structure data
Related structure data | 8c1rMC 8c1pC 8c1qC 8c1sC 8c2hC 8c2iC 8p3qC 8p3sC 8p3tC 8p3uC 8p3vC 8p3wC 8p3xC 8p3yC 8p3zC 8pivC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_16381.map.gz / Format: CCP4 / Size: 127.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.826 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_16381_msk_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_16381_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_16381_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Homomeric GluA2 F231A mutant AMPA receptor in complex with TARP g...
Entire | Name: Homomeric GluA2 F231A mutant AMPA receptor in complex with TARP gamma 2 |
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Components |
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-Supramolecule #1: Homomeric GluA2 F231A mutant AMPA receptor in complex with TARP g...
Supramolecule | Name: Homomeric GluA2 F231A mutant AMPA receptor in complex with TARP gamma 2 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #2, #1 |
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Source (natural) | Organism: Rattus (rat) |
-Macromolecule #1: Glutamate receptor 2
Macromolecule | Name: Glutamate receptor 2 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 99.880891 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MQKIMHISVL LSPVLWGLIF GDYKDDDDKV SSNSIQIGGL FPRGADQEYS AFRVGMVQFS TSEFRLTPHI DNLEVANSFA VTNAFCSQF SRGVYAIFGF YDKKSVNTIT SFCGTLHVSF ITPSFPTDGT HPFVIQMRPD LKGALLSLIE YYQWDKFAYL Y DSDRGLST ...String: MQKIMHISVL LSPVLWGLIF GDYKDDDDKV SSNSIQIGGL FPRGADQEYS AFRVGMVQFS TSEFRLTPHI DNLEVANSFA VTNAFCSQF SRGVYAIFGF YDKKSVNTIT SFCGTLHVSF ITPSFPTDGT HPFVIQMRPD LKGALLSLIE YYQWDKFAYL Y DSDRGLST LQAVLDSAAE KKWQVTAINV GNINNDKKDE TYRSLFQDLE LKKERRVILD CERDKVNDIV DQVITIGKHV KG YHYIIAN LGFTDGDLLK IQFGGANVSG FQIVDYDDSL VSKFIERWST LEEKEYPGAH TATIKYTSAL TYDAVQVMTE AFR NLRKQR IEISRRGNAG DCLANPAVPW GQGVEIERAL KQVQVEGLSG NIKFDQNGKR INYTINIMEL KTNGPRKIGY WSEV DKMVV TLTELPSGND TSGLENKTVV VTTILESPYV MMKKNHEMLE GNERYEGYCV DLAAEIAKHC GFKYKLTIVG DGKYG ARDA DTKIWNGMVG ELVYGKADIA IAPLTITLVR EEVIDFSKPF MSLGISIMIK KPQKSKPGVF SFLDPLAYEI WMCIVF AYI GVSVVLFLVS RFSPYEWHTE EFEDGRETQS SESTNEFGIF NSLWFSLGAF MRQGCDISPR SLSGRIVGGV WWFFTLI II SSYTANLAAF LTVERMVSPI ESAEDLSKQT EIAYGTLDSG STKEFFRRSK IAVFDKMWTY MRSAEPSVFV RTTAEGVA R VRKSKGKYAY LLESTMNEYI EQRKPCDTMK VGGNLDSKGY GIATPKGSSL GTPVNLAVLK LSEQGVLDKL KNKWWYDKG ECGAKDSGSK EKTSALSLSN VAGVFYILVG GLGLAMLVAL IEFCYKSRAE AKRMKVAKNP QNINPSSSQN SQNFATYKEG YNVYGIESV KI UniProtKB: Glutamate receptor 2 |
-Macromolecule #2: Voltage-dependent calcium channel gamma-2 subunit
Macromolecule | Name: Voltage-dependent calcium channel gamma-2 subunit / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 35.807555 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GLFDRGVQML LTTVGAFAAF SLMTIAVGTD YWLYSRGVCK TKSVSENETS KKNEEVMTHS GLWRTCCLEG NFKGLCKQID HFPEDADYE ADTAEYFLRA VRASSIFPIL SVILLFMGGL CIAASEFYKT RHNIILSAGI FFVSAGLSNI IGIIVYISAN A GDPSKSDS ...String: GLFDRGVQML LTTVGAFAAF SLMTIAVGTD YWLYSRGVCK TKSVSENETS KKNEEVMTHS GLWRTCCLEG NFKGLCKQID HFPEDADYE ADTAEYFLRA VRASSIFPIL SVILLFMGGL CIAASEFYKT RHNIILSAGI FFVSAGLSNI IGIIVYISAN A GDPSKSDS KKNSYSYGWS FYFGALSFII AEMVGVLAVH MFIDRHKQLR ATARATDYLQ ASAITRIPSY RYRYQRRSRS SS RSTEPSH SRDASPVGVK GFNTLPSTEI SMYTLSRDPL KAATTPTATY NSDRDNSFLQ VHNCIQKDSK DSLHANTANR RTT PV UniProtKB: Voltage-dependent calcium channel gamma-2 subunit |
-Macromolecule #3: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquino...
Macromolecule | Name: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid type: ligand / ID: 3 / Number of copies: 4 / Formula: ZK1 |
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Molecular weight | Theoretical: 409.254 Da |
Chemical component information | ChemComp-ZK1: |
-Macromolecule #4: PALMITIC ACID
Macromolecule | Name: PALMITIC ACID / type: ligand / ID: 4 / Number of copies: 7 / Formula: PLM |
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Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ChemComp-PLM: |
-Macromolecule #5: (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
Macromolecule | Name: (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / type: ligand / ID: 5 / Number of copies: 4 / Formula: OLC |
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Molecular weight | Theoretical: 356.54 Da |
Chemical component information | ChemComp-OLC: |
-Macromolecule #6: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 6 / Number of copies: 5 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ChemComp-POV: |
-Macromolecule #7: water
Macromolecule | Name: water / type: ligand / ID: 7 / Number of copies: 6 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.4000000000000001 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Details | Servalcat |
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Output model | PDB-8c1r: |