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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-12803 | |||||||||
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Title | NTD of resting state GluA1/A2 heterotertramer | |||||||||
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Function / homology | ![]() 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 / myosin V binding / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Trafficking of AMPA receptors / neuron spine ...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 / myosin V binding / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Trafficking of AMPA receptors / neuron spine / response to arsenic-containing substance / cellular response to dsRNA / dendritic spine membrane / Synaptic adhesion-like molecules / long-term synaptic depression / 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 / 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 / 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 / asymmetric synapse / G-protein alpha-subunit binding / regulation of receptor recycling / 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 / beta-2 adrenergic receptor binding / response to electrical stimulus / glutamate-gated calcium ion channel activity / glutamate-gated receptor 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 / dendrite cytoplasm / ionotropic glutamate receptor signaling pathway / SNARE binding / response to cocaine / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / long-term synaptic potentiation / protein tetramerization / cellular response to amino acid stimulus / postsynaptic density membrane / ionotropic glutamate receptor binding / 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 / receptor internalization / recycling endosome / response to toxic substance / cellular response to growth factor stimulus / cerebral cortex development / response to peptide hormone / small GTPase binding / synaptic vesicle membrane / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction / synaptic vesicle / response to estradiol / presynapse / signaling receptor activity / presynaptic membrane / amyloid-beta binding / early endosome membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
![]() | Zhang D / Watson JF / Matthews PM / Cais O / Greger IH | |||||||||
Funding support | 2 items
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![]() | ![]() Title: Gating and modulation of a hetero-octameric AMPA glutamate receptor. Authors: Danyang Zhang / Jake F Watson / Peter M Matthews / Ondrej Cais / Ingo H Greger / ![]() ![]() Abstract: AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning. A diverse array of AMPAR signalling complexes are ...AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1-GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. | |||||||||
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 | ![]() | 116.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13 KB 13 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.4 KB | Display | ![]() |
Images | ![]() | 115.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7occMC ![]() 7ocaC ![]() 7ocdC ![]() 7oceC ![]() 7ocfC 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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Voxel size | X=Y=Z: 1.07 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 : GluA1/A2 heterotertramer in complex with auxiliary subunits TARP ...
Entire | Name: GluA1/A2 heterotertramer in complex with auxiliary subunits TARP gamma 8 and CNIH2 |
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Components |
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-Supramolecule #1: GluA1/A2 heterotertramer in complex with auxiliary subunits TARP ...
Supramolecule | Name: GluA1/A2 heterotertramer in complex with auxiliary subunits TARP gamma 8 and CNIH2 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Glutamate receptor 1
Macromolecule | Name: Glutamate receptor 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 102.66193 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MPYIFAFFCT GFLGAVVGAD YKDDDDKNFP NNIQIGGLFP NQQSQEHAAF RFALSQLTEP PKLLPQIDIV NISDSFEMTY RFCSQFSKG VYAIFGFYER RTVNMLTSFC GALHVCFITP SFPVDTSNQF VLQLRPELQE ALISIIDHYK WQTFVYIYDA D RGLSVLQR ...String: MPYIFAFFCT GFLGAVVGAD YKDDDDKNFP NNIQIGGLFP NQQSQEHAAF RFALSQLTEP PKLLPQIDIV NISDSFEMTY RFCSQFSKG VYAIFGFYER RTVNMLTSFC GALHVCFITP SFPVDTSNQF VLQLRPELQE ALISIIDHYK WQTFVYIYDA D RGLSVLQR VLDTAAEKNW QVTAVNILTT TEEGYRMLFQ DLEKKKERLV VVDCESERLN AILGQIVKLE KNGIGYHYIL AN LGFMDID LNKFKESGAN VTGFQLVNYT DTIPARIMQQ WRTSDSRDHT RVDWKRPKYT SALTYDGVKV MAEAFQSLRR QRI DISRRG NAGDCLANPA VPWGQGIDIQ RALQQVRFEG LTGNVQFNEK GRRTNYTLHV IEMKHDGIRK IGYWNEDDKF VPAA TDAQA GGDNSSVQNR TYIVTTILED PYVMLKKNAN QFEGNDRYEG YCVELAAEIA KHVGYSYRLE IVSDGKYGAR DPDTK AWNG MVGELVYGRA DVAVAPLTIT LVREEVIDFS KPFMSLGISI MIKKPQKSKP GVFSFLDPLA YEIWMCIVFA YIGVSV VLF LVSRFSPYEW HSEEFEEGRD QTTSDQSNEF GIFNSLWFSL GAFMQQGCDI SPRSLSGRIV GGVWWFFTLI IISSYTA NL AAFLTVERMV SPIESAEDLA KQTEIAYGTL EAGSTKEFFR RSKIAVFEKM WTYMKSAEPS VFVRTTEEGM IRVRKSKG K YAYLLESTMN EYIEQRKPCD TMKVGGNLDS KGYGIATPKG SALRGPVNLA VLKLSEQGVL DKLKSKWWYD KGECGSKDS GSKDKTSALS LSNVAGVFYI LIGGLGLAML VALIEFCYKS RSESKRMKGF CLIPQQSINE AIRTSTLPRN SGAGASGGGG SGENGRVVS QDFPKSMQSI PCMSHSSGMP LGATGL |
-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: ![]() ![]() |
Molecular weight | Theoretical: 96.247055 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 SLGTPVNLAV LKLSEQGVLD KLKNKWWYDK GECGAKDSG SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR AEAKRMKVAK NPQNINPSSS |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 6 / 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 | 3 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE |
Details | Purified protein was incubated with 100 uM NBQX for at least 30 min on ice before freezing. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 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 |