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- EMDB-44132: Kainate receptor GluK2 in complex with agonist glutamate with asy... -
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Open data
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Basic information
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Title | Kainate receptor GluK2 in complex with agonist glutamate with asymmetric ligand-binding domain layer | |||||||||||||||
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![]() | kainate receptor / GluK2 / asymmetric / LBD / MEMBRANE PROTEIN | |||||||||||||||
Function / homology | ![]() mossy fiber rosette / detection of cold stimulus involved in thermoception / Activation of Na-permeable kainate receptors / kainate selective glutamate receptor complex / Activation of Ca-permeable Kainate Receptor / negative regulation of synaptic transmission, glutamatergic / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity / regulation of JNK cascade ...mossy fiber rosette / detection of cold stimulus involved in thermoception / Activation of Na-permeable kainate receptors / kainate selective glutamate receptor complex / Activation of Ca-permeable Kainate Receptor / negative regulation of synaptic transmission, glutamatergic / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity / regulation of JNK cascade / ubiquitin conjugating enzyme binding / receptor clustering / modulation of excitatory postsynaptic potential / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / neuronal action potential / behavioral fear response / positive regulation of synaptic transmission / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic modulation of chemical synaptic transmission / dendrite cytoplasm / hippocampal mossy fiber to CA3 synapse / regulation of membrane potential / SNARE binding / excitatory postsynaptic potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic transmission, glutamatergic / PDZ domain binding / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / modulation of chemical synaptic transmission / terminal bouton / intracellular calcium ion homeostasis / positive regulation of neuron apoptotic process / presynaptic membrane / scaffold protein binding / chemical synaptic transmission / postsynaptic membrane / perikaryon / neuron apoptotic process / negative regulation of neuron apoptotic process / postsynaptic density / axon / neuronal cell body / ubiquitin protein ligase binding / glutamatergic synapse / synapse / dendrite / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.84 Å | |||||||||||||||
![]() | Nadezhdin KD / Gangwar SP / Sobolevsky AI | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Kainate receptor channel opening and gating mechanism. Authors: Shanti Pal Gangwar / Maria V Yelshanskaya / Kirill D Nadezhdin / Laura Y Yen / Thomas P Newton / Muhammed Aktolun / Maria G Kurnikova / Alexander I Sobolevsky / ![]() Abstract: Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and ...Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism. Although structures of kainate receptor domains and subunit assemblies are available, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.3 KB 19.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.4 KB | Display | ![]() |
Images | ![]() | 126 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
Others | ![]() ![]() | 59.4 MB 59.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9b39MC ![]() 9b33C ![]() 9b34C ![]() 9b35C ![]() 9b36C ![]() 9b37C ![]() 9b38C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 1.3487 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_44132_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_44132_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : full-length rat GluK2 tetramer
Entire | Name: full-length rat GluK2 tetramer |
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Components |
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-Supramolecule #1: full-length rat GluK2 tetramer
Supramolecule | Name: full-length rat GluK2 tetramer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 410 KDa |
-Macromolecule #1: Glutamate receptor ionotropic, kainate 2
Macromolecule | Name: Glutamate receptor ionotropic, kainate 2 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 102.976586 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSF EASKKACDQL SLGVAAIFGP SHSSSANAVQ SICNALGVPH IQTRWKHQVS DNKDSFYVSL YPDFSSLSRA I LDLVQFFK ...String: MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSF EASKKACDQL SLGVAAIFGP SHSSSANAVQ SICNALGVPH IQTRWKHQVS DNKDSFYVSL YPDFSSLSRA I LDLVQFFK WKTVTVVYDD STGLIRLQEL IKAPSRYNLR LKIRQLPADT KDAKPLLKEM KRGKEFHVIF DCSHEMAAGI LK QALAMGM MTEYYHYIFT TLDLFALDVE PYRYSGVNMT GFRILNTENT QVSSIIEKWS MERLQAPPKP DSGLLDGFMT TDA ALMYDA VHVVSVAVQQ FPQMTVSSLQ CNRHKPWRFG TRFMSLIKEA HWEGLTGRIT FNKTNGLRTD FDLDVISLKE EGLE KIGTW DPASGLNMTE SQKGKPANIT DSLSNRSLIV TTILEEPYVL FKKSDKPLYG NDRFEGYCID LLRELSTILG FTYEI RLVE DGKYGAQDDV NGQWNGMVRE LIDHKADLAV APLAITYVRE KVIDFSKPFM TLGISILYRK PNGTNPGVFS FLNPLS PDI WMYVLLACLG VSCVLFVIAR FSPYEWYNPH PCNPDSDVVE NNFTLLNSFW FGVGALMQQG SELMPKALST RIVGGIW WF FTLIIISSYT ANLAAFLTVE RMESPIDSAD DLAKQTKIEY GAVEDGATMT FFKKSKISTY DKMWAFMSSR RQSVLVKS N EEGIQRVLTS DYAFLMESTT IEFVTQRNCN LTQIGGLIDS KGYGVGTPMG SPYRDKITIA ILQLQEEGKL HMMKEKWWR GNGCPEEESK EASALGVQNI GGIFIVLAAG LVLSVFVAVG EFLYKSKKNA QLEKRSFCSA MVEELRMSLK CQRRLKHKPQ APVIVKTEE VINMHTFNDR RLPGKETMAL VPR UniProtKB: Glutamate receptor ionotropic, kainate 2 |
-Macromolecule #5: GLUTAMIC ACID
Macromolecule | Name: GLUTAMIC ACID / type: ligand / ID: 5 / Number of copies: 4 / Formula: GLU |
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Molecular weight | Theoretical: 147.129 Da |
Chemical component information | ![]() ChemComp-GLU: |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 20 / 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
Buffer | pH: 8 Component:
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Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Support film - Material: GOLD / Support film - topology: HOLEY | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 5 / Number real images: 22990 / Average exposure time: 2.5 sec. / Average electron dose: 58.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | ![]() PDB-9b39: |