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Yorodumi- EMDB-44127: Open state of kainate receptor GluK2 in complex with agonist glut... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-44127 | |||||||||||||||
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Title | Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to one concanavalin A dimer | |||||||||||||||
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Sample |
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Keywords | kainate receptor / GluK2 / positive allosteric modulator / BPAM344 / open / concanavalin A / ConA / glutamate / MEMBRANE PROTEIN | |||||||||||||||
Biological species | Rattus norvegicus (Norway rat) / Canavalia ensiformis (jack bean) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.66 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_44127.map.gz | 59.7 MB | EMDB map data format | |
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Header (meta data) | emd-44127-v30.xml emd-44127.xml | 18.9 KB 18.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_44127_fsc.xml | 8.5 KB | Display | FSC data file |
Images | emd_44127.png | 64.3 KB | ||
Filedesc metadata | emd-44127.cif.gz | 6 KB | ||
Others | emd_44127_half_map_1.map.gz emd_44127_half_map_2.map.gz | 59.4 MB 59.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-44127 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44127 | HTTPS FTP |
-Validation report
Summary document | emd_44127_validation.pdf.gz | 896.7 KB | Display | EMDB validaton report |
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Full document | emd_44127_full_validation.pdf.gz | 896.3 KB | Display | |
Data in XML | emd_44127_validation.xml.gz | 16.3 KB | Display | |
Data in CIF | emd_44127_validation.cif.gz | 21 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44127 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44127 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_44127.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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: #1
File | emd_44127_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_44127_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : full-length rat GluK2 tetramer in complex with one concanavalin A...
Entire | Name: full-length rat GluK2 tetramer in complex with one concanavalin A homodimer |
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Components |
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-Supramolecule #1: full-length rat GluK2 tetramer in complex with one concanavalin A...
Supramolecule | Name: full-length rat GluK2 tetramer in complex with one concanavalin A homodimer type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 460 KDa |
-Supramolecule #2: Glutamate receptor ionotropic, kainate 2
Supramolecule | Name: Glutamate receptor ionotropic, kainate 2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: all |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
-Supramolecule #3: concanavalin A
Supramolecule | Name: concanavalin A / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Canavalia ensiformis (jack bean) |
-Macromolecule #1: Glutamate ionotropic receptor Kainate type subunit 2
Macromolecule | Name: Glutamate ionotropic receptor Kainate type subunit 2 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSFE ASKKACDQLS LGVAAIFGPS HSSSANAVQS ICNALGVPHI QTRWKHQVSD NKDSFYVSLY PDFSSLSRAI LDLVQFFKWK ...String: MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSFE ASKKACDQLS LGVAAIFGPS HSSSANAVQS ICNALGVPHI QTRWKHQVSD NKDSFYVSLY PDFSSLSRAI LDLVQFFKWK TVTVVYDDST GLIRLQELIK APSRYNLRLK IRQLPADTKD AKPLLKEMKR GKEFHVIFDC SHEMAAGILK QALAMGMMTE YYHYIFTTLD LFALDVEPYR YSGVNMTGFR ILNTENTQVS SIIEKWSMER LQAPPKPDSG LLDGFMTTDA ALMYDAVHVV SVAVQQFPQM TVSSLQCNRH KPWRFGTRFM SLIKEAHWEG LTGRITFNKT NGLRTDFDLD VISLKEEGLE KIGTWDPASG LNMTESQKGK PANITDSLSN RSLIVTTILE EPYVLFKKSD KPLYGNDRFE GYCIDLLREL STILGFTYEI RLVEDGKYGA QDDVNGQWNG MVRELIDHKA DLAVAPLAIT YVREKVIDFS KPFMTLGISI LYRKPNGTNP GVFSFLNPLS PDIWMYVLLA CLGVSCVLFV IARFSPYEWY NPHPCNPDSD VVENNFTLLN SFWFGVGALM QQGSELMPKA LSTRIVGGIW WFFTLIIISS YTANLAAFLT VERMESPIDS ADDLAKQTKI EYGAVEDGAT MTFFKKSKIS TYDKMWAFMS SRRQSVLVKS NEEGIQRVLT SDYAFLMEST TIEFVTQRNC NLTQIGGLID SKGYGVGTPM GSPYRDKITI AILQLQEEGK LHMMKEKWWR GNGCPEEESK EASALGVQNI GGIFIVLAAG LVLSVFVAVG EFLYKSKKNA QLEKRSFCSA MVEELRMSLK CQRRLKHKPQ APVIVKTEEV INMHTFNDRR LPGKETMALV PR |
-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: Ultra / Support film - Material: GOLD / Support film - topology: HOLEY | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN |
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 |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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