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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-8721 | ||||||||||||
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Title | Structure of AMPA receptor-TARP complex | ||||||||||||
![]() | protein complex | ||||||||||||
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Function / homology | ![]() 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 | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.9 Å | ||||||||||||
![]() | Chen S / Zhao Y / Wang YS / Shekhar M / Tajkhorshid E / Gouaux E | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Activation and Desensitization Mechanism of AMPA Receptor-TARP Complex by Cryo-EM. Authors: Shanshuang Chen / Yan Zhao / Yuhang Wang / Mrinal Shekhar / Emad Tajkhorshid / Eric Gouaux / ![]() Abstract: AMPA receptors mediate fast excitatory neurotransmission in the mammalian brain and transduce the binding of presynaptically released glutamate to the opening of a transmembrane cation channel. ...AMPA receptors mediate fast excitatory neurotransmission in the mammalian brain and transduce the binding of presynaptically released glutamate to the opening of a transmembrane cation channel. Within the postsynaptic density, however, AMPA receptors coassemble with transmembrane AMPA receptor regulatory proteins (TARPs), yielding a receptor complex with altered gating kinetics, pharmacology, and pore properties. Here, we elucidate structures of the GluA2-TARP γ2 complex in the presence of the partial agonist kainate or the full agonist quisqualate together with a positive allosteric modulator or with quisqualate alone. We show how TARPs sculpt the ligand-binding domain gating ring, enhancing kainate potency and diminishing the ensemble of desensitized states. TARPs encircle the receptor ion channel, stabilizing M2 helices and pore loops, illustrating how TARPs alter receptor pore properties. Structural and computational analysis suggests the full agonist and modulator complex harbors an ion-permeable channel gate, providing the first view of an activated AMPA receptor. | ||||||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 5.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.6 KB 13.6 KB | Display Display | ![]() |
Images | ![]() | 196.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 340.8 KB | Display | ![]() |
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Full document | ![]() | 340.4 KB | Display | |
Data in XML | ![]() | 5.9 KB | Display | |
Data in CIF | ![]() | 6.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5votMC ![]() 8722C ![]() 8723C ![]() 5vouC ![]() 5vovC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | protein complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.72 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Fully occupied GluA2 AMPA receptor - TARP complex bound with quis...
Entire | Name: Fully occupied GluA2 AMPA receptor - TARP complex bound with quisqualate and (R,R)-2b |
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Components |
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-Supramolecule #1: Fully occupied GluA2 AMPA receptor - TARP complex bound with quis...
Supramolecule | Name: Fully occupied GluA2 AMPA receptor - TARP complex bound with quisqualate and (R,R)-2b type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-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: ![]() ![]() |
Molecular weight | Theoretical: 99.530391 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ FSTSEFRLTP HIDNLEVANS FAVTNAFCSQ FSRGVYAIF GFYDKKSVNT ITSFCGTLHV SFITPSFPTD GTHPFVIQMR PDLKGALLSL IEYYQWDKFA YLYDSDRGLS T LQAVLDSA ...String: MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ FSTSEFRLTP HIDNLEVANS FAVTNAFCSQ FSRGVYAIF GFYDKKSVNT ITSFCGTLHV SFITPSFPTD GTHPFVIQMR PDLKGALLSL IEYYQWDKFA YLYDSDRGLS T LQAVLDSA AEKKWQVTAI NVGNINNDKK DETYRSLFQD LELKKERRVI LDCERDKVND IVDQVITIGK HVKGYHYIIA NL GFTDGDL LKIQFGGANV SGFQIVDYDD SLVSKFIERW STLEEKEYPG AHTATIKYTS ALTYDAVQVM TEAFRNLRKQ RIE ISRRGN AGDCLANPAV PWGQGVEIER ALKQVQVEGL SGNIKFDQNG KRINYTINIM ELKTNGPRKI GYWSEVDKMV VTLT ELPSG NDTSGLENKT VVVTTILESP YVMMKKNHEM LEGNERYEGY CVDLAAEIAK HCGFKYKLTI VGDGKYGARD ADTKI WNGM VGELVYGKAD IAIAPLTITL VREEVIDFSK PFMSLGISIM IKKPQKSKPG VFSFLDPLAY EIWMCIVFAY IGVSVV LFL VSRFSPYEWH TEEFEDGRET QSSESTNEFG IFNSLWFSLG AFMRQGCDIS PRSLSGRIVG GVWWFFTLII ISSYTAN LA AFLTVERMVS PIESAEDLSK QTEIAYGTLD SGSTKEFFRR SKIAVFDKMW TYMRSAEPSV FVRTTAEGVA RVRKSKGK Y AYLLESTMNE YIEQRKPCDT MKVGGNLDSK GYGIATPKGS SLGNAVNLAV LKLNEQGLLD KLKNKWWYDK GECGSGGGD SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR AEAKRMKVAK NPQNINPSSS QNSQNFATDY KDDDDKEGYN VYGIESVKI |
-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: ![]() ![]() |
Molecular weight | Theoretical: 35.938746 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3 mg/mL | ||||||||||||
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Buffer | pH: 8 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 54.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
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Output model | ![]() PDB-5vot: |