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- EMDB-44129: Open state of kainate receptor GluK2 in complex with agonist glut... -
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Open data
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Basic information
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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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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | ![]() ![]() | |||||||||||||||
![]() | 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 | ![]() | 55.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.9 KB 18.9 KB | Display Display | ![]() |
Images | ![]() | 122.7 KB | ||
Filedesc metadata | ![]() | 7.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9b36MC ![]() 9b33C ![]() 9b34C ![]() 9b35C ![]() 9b37C ![]() 9b38C ![]() 9b39C C: citing same article ( M: atomic model generated by this map |
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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
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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: ![]() ![]() ![]() |
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: ![]() ![]() ![]() |
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 #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: ![]() ![]() ![]() |
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 | ![]() |
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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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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
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 |
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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![]() 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: |