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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-8687 | |||||||||
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Title | GluA2-2xGSG1L bound to ZK | |||||||||
![]() | GluA2-2xGSG1L bound to ZK | |||||||||
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Function / homology | ![]() regulation of postsynaptic neurotransmitter receptor activity / regulation of AMPA receptor activity / regulation of postsynaptic neurotransmitter receptor internalization / spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / perisynaptic space / AMPA glutamate receptor activity / ligand-gated monoatomic cation channel activity ...regulation of postsynaptic neurotransmitter receptor activity / regulation of AMPA receptor activity / regulation of postsynaptic neurotransmitter receptor internalization / spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / perisynaptic space / AMPA glutamate receptor activity / ligand-gated monoatomic cation channel activity / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / immunoglobulin binding / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / cellular response to glycine / asymmetric synapse / regulation of receptor recycling / Unblocking of NMDA receptors, glutamate binding and activation / positive regulation of synaptic transmission / glutamate receptor binding / extracellular ligand-gated monoatomic ion channel activity / glutamate-gated receptor activity / glutamate-gated calcium ion channel 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 binding / dendrite cytoplasm / ionotropic glutamate receptor signaling pathway / SNARE binding / dendritic shaft / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / protein tetramerization / postsynaptic density membrane / modulation of chemical synaptic transmission / establishment of protein localization / Schaffer collateral - CA1 synapse / terminal bouton / receptor internalization / cerebral cortex development / synaptic vesicle membrane / synaptic vesicle / presynapse / signaling receptor activity / presynaptic membrane / 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 / 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: 4.6 Å | |||||||||
![]() | Twomey EC / Yelshanskaya MV / Grassucci RA / Frank J / Sobolevsky AI | |||||||||
![]() | ![]() Title: Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes. Authors: Edward C Twomey / Maria V Yelshanskaya / Robert A Grassucci / Joachim Frank / Alexander I Sobolevsky / ![]() Abstract: Fast excitatory neurotransmission is mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). AMPARs, localized at post-synaptic densities, are regulated by transmembrane auxiliary subunits ...Fast excitatory neurotransmission is mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). AMPARs, localized at post-synaptic densities, are regulated by transmembrane auxiliary subunits that modulate AMPAR assembly, trafficking, gating, and pharmacology. Aberrancies in AMPAR-mediated signaling are associated with numerous neurological disorders. Here, we report cryo-EM structures of an AMPAR in complex with the auxiliary subunit GSG1L in the closed and desensitized states. GSG1L favors the AMPAR desensitized state, where channel closure is facilitated by profound structural rearrangements in the AMPAR extracellular domain, with ligand-binding domain dimers losing their local 2-fold rotational symmetry. Our structural and functional experiments suggest that AMPAR auxiliary subunits share a modular architecture and use a common transmembrane scaffold for distinct extracellular modules to differentially regulate AMPAR gating. By comparing the AMPAR-GSG1L complex structures, we map conformational changes accompanying AMPAR recovery from desensitization and reveal structural bases for regulation of synaptic transmission by auxiliary subunits. | |||||||||
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 | ![]() | 14.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.8 KB 11.8 KB | Display Display | ![]() |
Images | ![]() | 23.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5vhyMC ![]() 8685C ![]() 8686C ![]() 8688C ![]() 5vhwC ![]() 5vhxC ![]() 5vhzC 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 | GluA2-2xGSG1L bound to ZK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.04 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 : GluA2-2xGSG1L ZK cryo-EM density
Entire | Name: GluA2-2xGSG1L ZK cryo-EM density |
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Components |
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-Supramolecule #1: GluA2-2xGSG1L ZK cryo-EM density
Supramolecule | Name: GluA2-2xGSG1L ZK cryo-EM density / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Glutamate receptor 2,Germ cell-specific gene 1-like protein
Macromolecule | Name: Glutamate receptor 2,Germ cell-specific gene 1-like protein type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 117.471211 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: NSIQIGGLFP RGADQEYSAF RVGMVQFSTS EFRLTPHIDN LEVANSFAVT NAFCSQFSRG VYAIFGFYDK KSVNTITSFC GTLHVSFIT PSFPTDGTHP FVIQMRPDLK GALLSLIEYY QWDKFAYLYD SDRGLSTLQA VLDSAAEKKW QVTAINVGNI N NDKKDETY ...String: NSIQIGGLFP RGADQEYSAF RVGMVQFSTS EFRLTPHIDN LEVANSFAVT NAFCSQFSRG VYAIFGFYDK KSVNTITSFC GTLHVSFIT PSFPTDGTHP FVIQMRPDLK GALLSLIEYY QWDKFAYLYD SDRGLSTLQA VLDSAAEKKW QVTAINVGNI N NDKKDETY RSLFQDLELK KERRVILDCE RDKVNDIVDQ VITIGKHVKG YHYIIANLGF TDGDLLKIQF GGAEVSGFQI VD YDDSLVS KFIERWSTLE EKEYPGAHTA TIKYTSALTY DAVQVMTEAF RNLRKQRIEI SRRGNAGDCL ANPAVPWGQG VEI ERALKQ VQVEGLSGNI KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVLTED DTSGLEQKTV VVTTILESPY VMMK KNHEM LEGNERYEGY CVDLAAEIAK HCGFKYKLTI VGDGKYGARD ADTKIWNGMV GELVYGKADI AIAPLTITLV REEVI DFSK PFMSLGISIM IKKPQKSKPG VFSFLDPLAY EIWMCIVFAY IGVSVVLFLV SRFSPYEWHT EEFEDGRETQ SSESTN EFG IFNSLWFSLG AFMQQGCDIS PRSLSGRIVG GVWWFFTLII ISSYTANLAA FLTVERMVSP IESAEDLSKQ TEIAYGT LD SGSTKEFFRR SKIAVFDKMW TYMRSAEPSV FVRTTAEGVA RVRKSKGKYA YLLESTMNEY IEQRKPCDTM KVGGNLDS K GYGIATPKGS SLGTPVNLAV LKLSEQGVLD KLKNKWWYDK GECGAKDSGS KEKTSALSLS NVAGVFYILV GGLGLAMLV ALIEFCYKSR AEAKRMKGTG KTSRRGRALL AVALNLLALL FATTAFLTTY WCQGTQRVPK PGCGQGGGAN CPNSGANATA NSTAAPVAA SPAGAPYSWE AGDERFQLRR FHTGIWYSCE EELGGPGEKC RSFIDLAPAS EKGVLWLSVV SEVLYILLLV V GFSLMCLE LLHSSSVIDG LKLNAFAAVF TVLSGLLGMV AHMMYTQVFQ VTVSLGPEDW RPHSWDYGWS FCLAWGSFTC CM AASVTTL NSYTKTVIEF |
-Macromolecule #2: {[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: 2 / Number of copies: 4 / Formula: ZK1 |
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Molecular weight | Theoretical: 409.254 Da |
Chemical component information | ![]() ChemComp-ZK1: |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 4 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 5 mg/mL |
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Buffer | pH: 8 |
Grid | Model: C-flat-1.2/1.3 / Material: GOLD / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE Details: Gold-gold grids, hydrogen and oxygen glow discharge (20s, 10 watts, 6.4 sccm H2, 27.5 sccm O2) |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV |
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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: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 42637 |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: ANGULAR RECONSTITUTION |