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Yorodumi- EMDB-44129: Open state of kainate receptor GluK2 in complex with agonist glut... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-44129 | |||||||||||||||
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Title | Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to two concanavalin A dimers. Composite map. | |||||||||||||||
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Sample |
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Keywords | kainate receptor / GluK2 / positive allosteric modulator / BPAM344 / open / concanavalin A / ConA / glutamate / MEMBRANE PROTEIN | |||||||||||||||
Function / homology | Function and homology information 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 / D-glucose binding / inhibitory postsynaptic potential / glutamate receptor activity ...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 / D-glucose binding / inhibitory postsynaptic potential / glutamate receptor activity / ubiquitin conjugating enzyme binding / receptor clustering / modulation of excitatory postsynaptic potential / D-mannose binding / regulation of JNK cascade / 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 / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic modulation of chemical synaptic transmission / excitatory postsynaptic potential / dendrite cytoplasm / hippocampal mossy fiber to CA3 synapse / SNARE binding / synaptic transmission, glutamatergic / regulation of membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / modulation of chemical synaptic transmission / terminal bouton / intracellular calcium ion homeostasis / vasodilation / positive regulation of neuron apoptotic process / presynaptic membrane / manganese ion binding / scaffold protein binding / chemical synaptic transmission / postsynaptic membrane / perikaryon / neuron apoptotic process / negative regulation of neuron apoptotic process / postsynaptic density / axon / neuronal cell body / glutamatergic synapse / synapse / ubiquitin protein ligase binding / dendrite / calcium ion binding / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | Rattus norvegicus (Norway rat) / Canavalia ensiformis (jack bean) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.29 Å | |||||||||||||||
Authors | Nadezhdin KD / Gangwar SP / Sobolevsky AI | |||||||||||||||
Funding support | United States, 4 items
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Citation | Journal: Nature / Year: 2024 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 | emd_44129.map.gz | 55.9 MB | EMDB map data format | |
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Header (meta data) | emd-44129-v30.xml emd-44129.xml | 18.9 KB 18.9 KB | Display Display | EMDB header |
Images | emd_44129.png | 122.7 KB | ||
Filedesc metadata | emd-44129.cif.gz | 7.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-44129 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44129 | HTTPS FTP |
-Related structure data
Related structure data | 9b36MC 9b33C 9b34C 9b35C 9b37C 9b38C 9b39C C: citing same article (ref.) M: atomic model generated by this map |
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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_44129.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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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
-Sample components
-Entire : full-length rat GluK2 tetramer in complex with two concanavalin A...
Entire | Name: full-length rat GluK2 tetramer in complex with two concanavalin A dimers |
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Components |
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-Supramolecule #1: full-length rat GluK2 tetramer in complex with two concanavalin A...
Supramolecule | Name: full-length rat GluK2 tetramer in complex with two concanavalin A dimers type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 510 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: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 102.976586 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 #2: Concanavalin A
Macromolecule | Name: Concanavalin A / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Canavalia ensiformis (jack bean) |
Molecular weight | Theoretical: 25.622385 KDa |
Sequence | String: ADTIVAVELD TYPNTDIGDP SYPHIGIDIK SVRSKKTAKW NMQNGKVGTA HIIYNSVDKR LSAVVSYPNA DSATVSYDVD LDNVLPEWV RVGLSASTGL YKETNTILSW SFTSKLKSNS THETNALHFM FNQFSKDQKD LILQGDATTG TDGNLELTRV S SNGSPQGS ...String: ADTIVAVELD TYPNTDIGDP SYPHIGIDIK SVRSKKTAKW NMQNGKVGTA HIIYNSVDKR LSAVVSYPNA DSATVSYDVD LDNVLPEWV RVGLSASTGL YKETNTILSW SFTSKLKSNS THETNALHFM FNQFSKDQKD LILQGDATTG TDGNLELTRV S SNGSPQGS SVGRALFYAP VHIWESSAVV ASFEATFTFL IKSPDSHPAD GIAFFISNID SSIPSGSTGR LLGLFPDAN UniProtKB: Concanavalin V |
-Macromolecule #10: 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-...
Macromolecule | Name: 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide type: ligand / ID: 10 / Number of copies: 4 / Formula: 2J9 |
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Molecular weight | Theoretical: 242.27 Da |
Chemical component information | ChemComp-2J9: |
-Macromolecule #11: GLUTAMIC ACID
Macromolecule | Name: GLUTAMIC ACID / type: ligand / ID: 11 / Number of copies: 4 / Formula: GLU |
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Molecular weight | Theoretical: 147.129 Da |
Chemical component information | ChemComp-GLU: |
-Macromolecule #12: (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: 12 / Number of copies: 14 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ChemComp-POV: |
-Macromolecule #13: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 13 / Number of copies: 8 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Macromolecule #14: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 14 / Number of copies: 4 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #15: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 15 / Number of copies: 4 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-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 |
-Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
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 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 8660229 |
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Startup model | Type of model: OTHER |
Initial angle assignment | Type: OTHER / Software - Name: cryoSPARC (ver. 4.4.1) |
Final angle assignment | Type: OTHER / Software - Name: cryoSPARC (ver. 4.4.1) |
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.29 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.4.1) Details: This is composite map. Reference map: 4.29 A ATD: 3.5 A LBD-TMD: 3.4 A ConA: 3.58 A Number images used: 109827 |
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | PDB-9b36: |